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1.
Int. j. morphol ; 38(2): 340-347, abr. 2020. tab, graf
Article in English | LILACS | ID: biblio-1056445

ABSTRACT

Diabetes mellitus is a serious disease with a high incidence of occurrence in our community. Gum Arabic (GA) is a branched-chain polysaccharide which has strong antioxidant properties, and has been used to reduce the experimental toxicity. Yet, the effects of GA on testicular tissue in type I diabetic rats have not been enough investigated. This study was designed to investigate histological changes in testes of male Wistar rats and investigate the protective potential of GA against diabetes- induced testicular toxicity in rats. Fifty adult male Wistar rats were assigned into five groups (n = 10 of each): Group 1 (non-diabetic rats) served as control, Group 2 served as diabetic group injected with Alloxan, Group 3 diabetic group plus insulin, Group 4 diabetic group given 15 % GA in drinking water and Group 5 diabetic group plus insulin and GA for 4 weeks. Compared to control group, histopathological examinations of testicular tissue from the diabetic rats group, showed degeneration, necrosis and atrophy of seminiferous with presence of giant cells. Necrosis and hemorrhage in the renal tissue. On the other hand, treatment with GA ameliorated all the previous histological changes. Overall, oral administration of GA alone or with insulin daily for 4 weeks successfully ameliorated the testicular histological changes. These data demonstrated that GA significantly improved diabetes complication in rat testis. This study suggested that GA might have a protective effect against oxidative stress-induced impaired testicular functions in diabetic rats. The possible mechanisms of this action might be ascribed to their antioxidant and anti-inflammatory properties.


La diabetes mellitus es una enfermedad grave con una alta incidencia en nuestra comunidad. La goma arábiga (GA) es un polisacárido con propiedades antioxidantes importantes, y se ha utilizado para reducir la toxicidad experimental. Sin embargo, los efectos de GA sobre el tejido testicular en ratas diabéticas tipo I no se ha investigado lo suficiente. El estudio fue diseñado para pesquisar los cambios histológicos en los testículos de ratas Wistar macho e investigar el potencial protector de GA contra la toxicidad testicular inducida por la diabetes en ratas. Fueron asignadas cincuenta ratas Wistar macho adultas en cinco grupos (n = 10 de cada una): el grupo 1 (ratas no diabéticas) sirvió como control, el grupo 2 sirvió como grupo diabético inyectado con Alloxan, grupo diabético del grupo 3 más insulina. El grupo 4 diabético recibió 15 % de GA en agua potable, y el grupo diabético 5 más insulina y GA durante 4 semanas. Al comparar con el grupo control, los exámenes histopatológicos del tejido testicular del grupo de ratas diabéticas mostraron degeneración, necrosis y atrofia de los túbulos seminíferos con presencia de células gigantes, necrosis y hemorragia en el tejido renal. Por otra parte, el tratamiento con GA mejoró todos los cambios histológicos previos. En general, la administración oral de GA solamente, o con insulina diariamente durante 4 semanas mejoró los cambios histológicos testiculares. Estos datos demostraron que GA mejoró significativamente los efectos de la diabetes en testículos de rata. Este estudio sugiere que GA podría tener un efecto protector contra las funciones testiculares deterioradas, inducidas por el estrés oxidativo en ratas diabéticas. Los posibles mecanismos de esta acción podrían atribuirse a sus propiedades antioxidantes y antiinflamatorias.


Subject(s)
Animals , Male , Rats , Testis/drug effects , Gum Arabic/pharmacology , Insulin/pharmacology , Rats, Wistar , Diabetes Mellitus, Experimental/drug therapy , Gum Arabic/administration & dosage
2.
Braz. j. med. biol. res ; 51(4): e6980, 2018. graf
Article in English | LILACS | ID: biblio-889067

ABSTRACT

Hormones regulate hepatic gene expressions to maintain metabolic homeostasis. Ectonucleotide pyrophosphatase/phosphodiesterase 1 has been thought to interfere with insulin signaling. To determine its potential role in the regulation of metabolism, we analyzed its gene (Enpp1) expression in the liver of rats experiencing fasting and refeeding cycles, and in primary rat hepatocytes and human hepatoma HepG2 cells treated with insulin and dexamethasone using northern blot and real-time PCR techniques. Hepatic Enpp1 expression was induced by fasting and reduced by refeeding in the rat liver. In primary rat hepatocytes and HepG2 hepatoma cells, insulin reduced Enpp1 mRNA abundance, whereas dexamethasone induced it. Dexamethasone disrupted the insulin-reduced Enpp1 expression in primary hepatocytes. This is in contrast to the responses of the expression of the cytosolic form of phosphoenolpyruvate carboxykinase gene to the same hormones, where insulin reduced it significantly in the process. In addition, the dexamethasone-induced Enpp1 gene expression was attenuated in the presence of 8-Br-cAMP. In conclusion, we demonstrated for the first time that hepatic Enpp1 is regulated in the cycle of fasting and refeeding, a process that might be attributed to insulin-reduced Enpp1 expression. This insulin-reduced Enpp1 expression might play a role in the development of complications in diabetic patients.


Subject(s)
Humans , Animals , Male , Rats , Pyrophosphatases/genetics , RNA, Messenger/drug effects , Dexamethasone/pharmacology , Phosphoric Diester Hydrolases/genetics , Glucocorticoids/pharmacology , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Liver/enzymology , Pyrophosphatases/biosynthesis , Pyrophosphatases/drug effects , Insulin Resistance , RNA, Messenger/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Enzyme Induction/drug effects , Fasting/metabolism , Rats, Sprague-Dawley , Phosphoric Diester Hydrolases/biosynthesis , Phosphoric Diester Hydrolases/drug effects , Hep G2 Cells , Real-Time Polymerase Chain Reaction
3.
An. acad. bras. ciênc ; 89(3): 1699-1705, July-Sept. 2017. graf
Article in English | LILACS | ID: biblio-886771

ABSTRACT

ABSTRACT Introduction/Aim: The gut has shown to have a pivotal role on the pathophysiology of metabolic disease. Food stimulation of distal intestinal segments promotes enterohormones secretion influencing insulin metabolism. In diabetic rats, oral insulin has potential to change intestinal epithelium behavior. This macromolecule promotes positive effects on laboratorial metabolic parameters and decreases diabetic intestinal hypertrophy. This study aims to test if oral insulin can influence metabolic parameters and intestinal weight in obese non-diabetic rats. Methods: Twelve weeks old Wistar rats were divided in 3 groups: control (CTRL) standard chow group; high fat diet low carbohydrates group (HFD) and HFD plus daily oral 20U insulin gavage (HFD+INS). Weight and food consumption were weekly obtained. After eight weeks, fasting blood samples were collected for laboratorial analysis. After euthanasia gut samples were isolated. Results: Rat oral insulin treatment decreased body weight gain (p<0,001), fasting glucose and triglycerides serum levels (p<0,05) an increased intestinal weight of distal ileum (P<0,05). Animal submitted to high fat diet presented higher levels of HOMA-IR although significant difference to CT was not achieved. HOMA-beta were significantly higher (p<0.05) in HFD+INS. Visceral fat was 10% lower in HFD+INS but the difference was not significant. Conclusions: In non-diabetic obese rats, oral insulin improves metabolic malfunction associated to rescue of beta-cell activity.


Subject(s)
Animals , Male , Rats , Blood Glucose/analysis , Weight Loss/drug effects , Diet, High-Fat , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Lipids/blood , Blood Glucose/drug effects , Radioimmunoassay , Rats, Wistar , Hypoglycemic Agents/pharmacology , Insulin/pharmacology
4.
Arq. bras. cardiol ; 108(5): 436-442, May 2017. tab, graf
Article in English | LILACS | ID: biblio-838740

ABSTRACT

Abstract Background: Resistance exercise (RE) has been recommended for patients with cardiovascular diseases. Recently, a few studies have demonstrated that the intensity of a single bout of RE has an effect on endothelial adaptations to exercise. However, there is no data about the effects of different volumes of RE on endothelium function. Objective: The aim of the study was to evaluate the effects of different volumes of RE in a single bout on endothelium-dependent vasodilatation and nitric oxide (NO) synthesis in the mesenteric artery of healthy animals. Methods: Male Wistar rats were divided into three groups: Control (Ct); low-volume RE (LV, 5 sets x 10 repetitions) and high-volume RE (HV, 15 sets x 10 repetitions). The established intensity was 70% of the maximal repetition test. After the exercise protocol, rings of mesenteric artery were used for assessment of vascular reactivity, and other mesenteric arteries were prepared for detection of measure NO production by DAF-FM fluorescence. Insulin responsiveness on NO synthesis was evaluated by stimulating the vascular rings with insulin (10 nM). Results: The maximal relaxation response to insulin increased in the HV group only as compared with the Ct group. Moreover, the inhibition of nitric oxide synthesis (L-NAME) completely abolished the insulin-induced vasorelaxation in exercised rats. NO production showed a volume-dependent increase in the endothelial and smooth muscle layer. In endothelial layer, only Ct and LV groups showed a significant increase in NO synthesis when compared to their respective group under basal condition. On the other hand, in smooth muscle layer, NO fluorescence increased in all groups when compared to their respective group under basal condition. Conclusions: Our results suggest that a single bout of RE promotes vascular endothelium changes in a volume-dependent manner. The 15 sets x 10 repetitions exercise plan induced the greatest levels of NO synthesis.


Resumo Fundamentos: O exercício resistido (ER) tem sido recomendado para pacientes com doenças cardiovasculares. Recentemente, alguns estudos demonstraram que a intensidade de uma sessão de ER exerce um efeito sobre a disfunção endotelial. No entanto, não há dados sobre os efeitos de diferentes volumes de ER sobre a função endotelial. Objetivo: O objetivo deste estudo foi avaliar os efeitos de diferentes volumes de ER, realizados em uma única sessão, sobre a vasodilatação dependente do endotélio e síntese de óxido nítrico (NO) em artéria mesentérica de animais saudáveis. Métodos: Ratos Wistar machos foram divididos em três grupos: Controle (Ct); baixo volume (BV, 5 séries x 10 repetições) e alto volume de ER (AV, 15 séries x 10 repetições). Foi estabelecida a intensidade de 70% do teste de repetição máxima. Após o protocolo de exercício, anéis de artéria mesentérica foram utilizados na avaliação da reatividade vascular, e outras artérias mesentéricas foram preparadas para a detecção da produção de NO por fluorescência com para do DAF-FM. A resposta à insulina pela síntese de NO foi avaliada estimulando-se os anéis vasculares com insulina (10nM). Resultados: A resposta máxima do relaxamento induzido por insulina foi aumentada somente no grupo AV em comparação ao grupo Ct. Além disso, a inibição da síntese do NO (L-NAME), aboliu completamente o relaxamento vascular induzido por insulina em ratos exercitados. A produção de NO mostrou um aumento dependente do volume no endotélio e no músculo liso. No endotélio, apenas os grupos Ct e BV mostraram aumento significativo na síntese de NO quando comparado aos seus respectivos grupos sob condição basal. No entanto, no músculo liso, a fluorescência foi aumentada em todos os grupos quando comparados aos seus respectivos grupos sob a condição basal. Conclusões: Nossos resultados sugerem que uma única sessão de ER foi capaz de promover adaptações no endotélio vascular. Além disso, nós observamos que este efeito é volume-dependente e o volume de 15 séries x10 repetições induziu o maior aumento na síntese de NO.


Subject(s)
Animals , Male , Physical Conditioning, Animal/physiology , Endothelium, Vascular/physiology , Endothelium-Dependent Relaxing Factors/physiology , Resistance Training , Nitric Oxide/physiology , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Endothelium, Vascular/drug effects , Random Allocation , Rats, Wistar , NG-Nitroarginine Methyl Ester/pharmacology , Enzyme Inhibitors/pharmacology , Insulin/pharmacology , Mesenteric Arteries/drug effects , Mesenteric Arteries/physiology
5.
Rev. bras. enferm ; 70(1): 7-14, jan.-fev. 2017. tab, graf
Article in Portuguese | LILACS, BDENF | ID: biblio-843603

ABSTRACT

RESUMO Objetivo: descrever o processo de construção de uma cartilha educativa sobre insulinoterapia para crianças com diabetes mellitus tipo 1. Método: abordagem metodológica, na qual se seguiram as etapas: seleção do conteúdo e tipo de tecnologia a ser construída (para essa etapa, foi realizada revisão integrativa, análises dos comentários de blogs sobre Diabetes Mellitus tipo 1 e entrevista com as crianças), criação de imagens, diagramação e composição do layout. Resultados: o trabalho resultou na produção da versão final da cartilha educativa, que teve como título Aplicando a insulina: a aventura de Beto. O processo de construção da cartilha foi embasado na participação ativa das crianças e norteado pelo referencial teórico do Construtivismo Piagetiano. Conclusão: o recurso é facilitador para a melhoria do conhecimento e das práticas de autocuidado de crianças com Diabetes Mellitus tipo 1.


RESUMEN Objetivo: describir el proceso de construcción de una cartilla educativa sobre insulinoterapia para niños con diabetes mellitus tipo 1. Método: abordaje metodológico en el que unas etapas fueron seguidas: selección de contenido y tipo de tecnología a ser construida (para esa etapa, se realizó una revisión integrativa, análisis de comentarios de blogs sobre Diabetes Mellitus tipo 1 y entrevista con los niños), creación de imágenes, diagramación y composición de layout. Resultados: el trabajo resultó en la producción de una versión final de una cartilla educativa, cuyo título fue Aplicando la insulina: la aventura de Beto. El proceso de construcción de la cartilla se basó en la participación activa de los niños y se norteó por el referencial teórico del Constructivismo Piagetiano. Conclusión: el recurso es facilitador para la mejoría del conocimiento y de las prácticas de autocuidado de niños con Diabetes Mellitus tipo 1.


ABSTRACT Objective: to describe the process of developing of an educational booklet on insulin therapy for children with diabetes mellitus type 1. Method: methodological approach, in which the following steps were carried out: selecting of the content and type of technology to be developed (for this step, an integrative review, an analysis of the comments of blogs about Diabetes Mellitus type 1 and interviews with the children were performed), creation of images, formatting and layout composition. Results: the work resulted in the production of the final version of the educational booklet, which was titled Aplicando a insulina: a aventura de Beto [Applying insulin: Beto's adventure]. The process of developing of the booklet was based on the active participation of the children and guided by the theoretical framework of Piagetian Constructivism. Conclusion: the resource is a facilitator for the improvement of the knowledge and practices of self care of children with Diabetes Mellitus type 1.


Subject(s)
Humans , Child, Preschool , Child , Adolescent , Pamphlets , Self Care/methods , Patient Education as Topic/methods , Program Development/methods , Diabetes Mellitus, Type 1/drug therapy , Hyperglycemia/drug therapy , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/pharmacology , Insulin/therapeutic use , Insulin/pharmacology
6.
Med. interna (Caracas) ; 33(1): 4-18, 2017. ilus, tab, graf
Article in Spanish | LILACS, LIVECS | ID: biblio-1009223

ABSTRACT

Por muchos años, la metformina se ha consolidado como el principal pilar del tratamiento de la diabetes mellitus; sin embargo, los aspectos de su mecanismo de acción han permanecido mal definidos. Avances recientes han revelado que esta droga, además de su propiedad de reducir la glucemia, puede ser promisoria para identificar blancos metabólicos entre la señalización metabólica normal y anormal. El centro del mecanismo de acción de la metformina es la alteración del metabolismo energético de la célula, de tal forma que su efecto hipoglucemiante ocurre por inhibición de la gluconeogénesis hepática, opuesto a la acción del glucagón. La inhibición del complejo I mitocondrial resulta en defectos en AMPc y señalización de la protein cinasa A en respuesta al glucagón. La estimulación de la protein cinasa activada 5'AMP, aunque dispensable para el efecto hipoglucemiante de la metformina, confiere sensibilidad a la insulina, principalmente por modulación del metabolismo lipídico. Conjuntamente con su efecto hipoglucemiante se ha despertado interés en las potenciales acciones relevantes sobre las enfermedades cardiovasculares y cáncer. No obstante, tales mecanismos de acción permanecen esquivos. La data convincente coloca al metabolismo energético en el centro del mecanismo de acción de la metformina en la diabetes y también puede jugar un papel importante en las enfermedades cardiovasculares y cáncer. En esta revisión se discute el conocimiento actualizados de la acción antigluconeogénica de la metformina y sus implicaciones en el descubrimiento de nuevos objetivos(AU)


Metformin has been the mainstay of therapy for diabetes mellitus for many years; however, the aspects of its action remained ill defined. Recent advances revealed that this drug, in addition to its glucose-lowering action, might be promising for specifically targeting metabolic differences between normal and abnormal metabolic signaling. The knowledge gained from dissecting the principal mechanisms by which metformin works can help us develop novel treatments. The center of metformin's mechanism of action is the alteration of the energy metabolism of the cell. Metformin exerts its prevailing, glucose-lowering effect by inhibiting hepatic gluconeogenesis and opposing the action of glucagon. The inhibition of mitochondrial complex I results in defective cAMP and protein kinase A signalling in response to glucagon. Stimulation of 5'-AMP-activated protein kinase, although dispensable for the glucose-lowering effect of metformin, confers insulin sensitivity, mainly by modulating lipid metabolism. Besides its glucose-lowering effect, there is interest in actions of the drug of potential relevance to cardiovascular diseases and cancer. However, the underlying mechanisms of action remain elusive. Convincing data place energy metabolism at the center of metformin's mechanism of action in diabetes and may also be of importance in cardiovascular diseases and cancer. Here, we discuss the updated understanding of the antigliconeogenic action of metformin in the liver and the implications of the discoveries of metformin targets for the treatment of diabetes mellitus and cancer(AU)


Subject(s)
Humans , Male , Female , Diabetes Mellitus/physiopathology , Diabetes Mellitus/drug therapy , Metformin/administration & dosage , Insulin/pharmacology , Internal Medicine , Metabolic Diseases
7.
Arq. bras. oftalmol ; 79(2): 105-110, Mar.-Apr. 2016. tab, graf
Article in English | LILACS | ID: lil-782803

ABSTRACT

ABSTRACT Purpose: The goal of the present study was to establish a protocol for primary culture of lacrimal gland acinar cells (LGACs) and to assess the effect of adding insulin to the culture media. Methods: LGACs were isolated and cultured from lacrimal glands of Wistar male rats. The study outcomes included cell number, viability, and peroxidase release over time and in response to three concentrations of insulin (0.5, 5.0, and 50.0 μg/mL). Results: In LGAC primary culture, cells started to form clusters by day 3. There was a time-response pattern of peroxidase release, which rose by day 6, in response to carbachol. Culture viability lasted for 12 days. An insulin concentration of 5.0 μg/mL in the culture medium resulted in higher viability and secretory capacity. Conclusions: The present method simplifies the isolation and culture of LGACs. The data confirmed the relevance of adding insulin to maintain LGACs in culture.


RESUMO Objetivo: O objetivo do estudo foi estabelecer um protocolo de cultura primária para o isolamento de células acinares da glândula lacrimal (CAGL) e avaliar a relevância de insulina no meio de cultura. Métodos: CAGL foram isoladas e cultivadas a partir das glândulas lacrimais de ratos Wistar machos. Os parâmetros analisados foram: o número de células, viabilidade e secreção da peroxidase ao longo do tempo e em resposta a três concentrações de insulina (0,5; 5,0 e 50,0 μg/ml). Resultados: Na cultura primária de CAGL as células passaram a se agrupar por volta do dia 3. A secreção de peroxidase em resposta ao carbacol aumentou no dia 6. O período de cultura viável foi limitado à 12 dias. Insulina à 5,0 μg/ml no meio de cultura resultou em viabilidade e capacidade secretora maior. Conclusão: o estudo descreveu um método para simplificar o isolamento e cultivo de CAGL. Os dados apresentados confirmam a importância da insulina na manutenção da cultura de CAGL.


Subject(s)
Animals , Male , Acinar Cells/cytology , Primary Cell Culture/standards , Insulin/pharmacology , Lacrimal Apparatus/cytology , Carbachol/metabolism , Cell Count/methods , Cell Separation/methods , Rats, Wistar , Peroxidase/metabolism , Acinar Cells/drug effects , Acinar Cells/metabolism , Insulin/metabolism , Lacrimal Apparatus/metabolism
8.
Clinics ; 70(8): 569-576, 08/2015. tab, graf
Article in English | LILACS | ID: lil-753961

ABSTRACT

OBJECTIVE: The aim of this study was to determine the in vitro effect of glutamine and insulin on apoptosis, mitochondrial membrane potential, cell permeability, and inflammatory cytokines in hyperglycemic umbilical vein endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells were grown and subjected to glutamine and insulin to examine the effects of these agents on the hyperglycemic state. Mitochondrial function and the production of inflammatory cytokines were assessed using fluorescence analysis and multiple cytotoxicity assays. Apoptosis was analyzed by the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay. RESULTS: Glutamine maintains the integrity of the mitochondria by reducing the cell permeability and cytochrome c levels and increasing the mitochondrial membrane potential. The cytochrome c level was significantly (p<0.005) reduced when the cells were treated with glutamine. An apoptosis assay revealed significantly reduced apoptosis (p<0.005) in the glutamine-treated cells. Moreover, glutamine alone or in combination with insulin modulated inflammatory cytokine levels. Interleukin-10, interleukin-6, and vascular endothelial growth factor were up-regulated while tumor necrosis factor-α was down-regulated after treatment with glutamine. CONCLUSION: Glutamine, either alone or in combination with insulin, can positively modulate the mitochondrial stress and cell permeability in umbilical vein endothelial cells. Glutamine regulates the expression of inflammatory cytokines and maintains the balance of the mitochondria in a cytoprotective manner. .


Subject(s)
Humans , Apoptosis/drug effects , Glutamine/pharmacology , Hyperglycemia/drug therapy , Mitochondria/drug effects , Oxidative Stress/drug effects , Cells, Cultured , Cell Membrane Permeability/drug effects , Cytochromes c/analysis , Cytokines/analysis , Cytokines/drug effects , Drug Combinations , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Hyperglycemia/metabolism , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Mitochondria/metabolism
9.
Arq. bras. oftalmol ; 78(3): 158-163, May-Jun/2015. tab, graf
Article in English | LILACS | ID: lil-753015

ABSTRACT

ABSTRACT Purpose: In the lacrimal gland (LG) acinar cells, signaling regulates the release of secretory vesicles through specific Rab and SNARE exocytotic proteins. In diabetes mellitus (DM), the LGs are dysfunctional. The aim of this work was to determine if secretory apparatus changes were associated with any effects on the secretory vesicles (SV) in diabetic rats as well as the expression levels of constituent Rab and members of the SNARE family, and if insulin supplementation reversed those changes. Methods: DM was induced in male Wistar rats with an intravenous dose of streptozotocin (60 mg/kg). One of the two diabetic groups was then treated every other day with insulin (1 IU). A third control group was injected with vehicle. After 10 weeks, Western blotting and RT-PCR were used to compared the Rab and SNARE secretory factor levels in the LGs. Transmission electron microscopy evaluated acinar cell SV density and integrity. Results: In the diabetes mellitus group, there were fewer and enlarged SV. The Rab 27b, Rab 3d, and syntaxin-1 protein expression declined in the rats with diabetes mellitus. Insulin treatment restored the SV density and the Rab 27b and syntaxin expression to their control protein levels, whereas the Vamp 2 mRNA expression increased above the control levels. Conclusions: Diabetes mellitus LG changes were associated with the declines in protein expression levels that were involved in supporting exocytosis and vesicular formation. They were partially reversed by insulin replacement therapy. These findings may help to improve therapeutic management of dry eye in diabetes mellitus. .


RESUMO Objetivo: Células acinares da glândula lacrimal (GL) sinalizam a regulação da liberação através de vesículas secretórias específicas Rab proteínas exocitóticas SNARE. No diabetes mellitus (DM), as glândulas lacrimais são disfuncionais. O objetivo deste trabalho foi determinar se em ratos diabéticos, alterações dos aparatos secretórios estão associados a efeitos sobre vesículas secretoras (VS) e sobre os níveis de expressão do constituinte Rab, bem como membros da família SNARE, e se a suplementação de insulina reverte as alterações. Métodos: DM foi induzido em ratos Wistar machos com uma dose intravenosa de estreptozotocina (60 mg/kg). Um dos dois grupos diabéticos foi então tratado a cada dois dias com insulina (1 UI). Um terceiro grupo controle foi injetado com o veículo. Após 10 semanas, western blot e RT-PCR comparou níveis de fatores secretórios de Rab e SNARE na glândula lacrimal. Microscopia eletrônica de transmissão (MET) avaliaram a densidade e integridade de VS de célula acinar. Resultados: No grupo diabetes mellitus , houve poucas e alargadas VS. Rab27b, Rab 3d e Sintaxina-1 diminuiu a expressão da proteína em ratos com Diabetes Mellitus. O tratamento com insulina restaurou a densidade das VS e expressão de Rab 27b e Sintaxina para seus níveis de proteína controle, enquanto a expressão de Vamp 2 RNAm aumentou em relação aos controles. Conclusões: Alterações na glândula lacrimal de diabetes mellitus estão associadas a reduções nos níveis de expressão de proteínas envolvidas no apoio a exocitose e formação vesicular. Eles são, em parte, revertida por terapia de reposição de insulina. Estes resultados podem ajudar a melhorar a conduta terapêutica do olho seco no diabetes mellitus. .


Subject(s)
Animals , Male , Diabetes Mellitus, Experimental/metabolism , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Lacrimal Apparatus/drug effects , Secretory Vesicles/metabolism , Acetylcholine/analysis , Acinar Cells/ultrastructure , Blotting, Western/methods , Diabetes Mellitus, Experimental/chemically induced , Exocytosis/drug effects , Lacrimal Apparatus , Models, Animal , Qa-SNARE Proteins/metabolism , R-SNARE Proteins/metabolism , Rats, Wistar , RNA, Messenger/metabolism , Secretory Vesicles/drug effects , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolism
10.
Acta cir. bras ; 29(2): 125-131, 02/2014. tab, graf
Article in English | LILACS | ID: lil-702526

ABSTRACT

To analyze the effects of application of 1% and 3% insulin-like growth factor I (IGF-1) cream on the process of wound healing in induced skin lesions in diabetic and non-diabetic rats and evaluate its effect on expression of myofibroblasts. METHODS: Ninety-six Wistar adult male rats were divided into six groups, with 16 rats in each group, as follows: group 1: non-diabetic, untreated; group 2: non-diabetic, treated with 1% IGF-1 cream; group 3: non-diabetic, treated with 3% IGF-1 cream; group 4: diabetic, untreated; group 5: diabetic, treated with 1% IGF-1 cream; and group 6: diabetic, treated with 3% IGF-1 cream. In groups 4, 5, and 6, diabetes was induced by intravenous injection of alloxan. After diabetes had been induced, animals were mantained for 3 months. The experimental procedure consisted of the creation of a circular incision of 0.9 mm in diameter using a metal punch. Following this, wounds were treated daily according to the assigned treatment regimen. Groups 2 and 5 were treated with 1% IGF-1 cream, groups 3 and 6 with 3% IGF-1 cream, and groups 1 and 4 and the untreated groups with 0.9% saline solution. From each group, samples from 4 rats were taken at three, seven, 14, and 21 days after the injury. Samples were fixed in 10% formalin to prepare slides for histological analysis. Slides stained with hematoxylin-eosin (H&E) and Masson were observed vascular proliferation, mononuclear cells, polymorphonuclear cells, fibroblast proliferation, re-epithelialization, and collagen fibers. This study analyzed the expression of α-smooth muscle actin using specific antibodies to correlate the temporal expression of α-smooth muscle-specific actin (α-SM actin), a molecular marker for myofibroblast transformation. RESULTS: Macroscopic observation of wounds showed a more rapid re-epithelialization of wounds treated with IGF. Regarding acute inflammatory reactions, the results of the analysis of vascular.


Subject(s)
Animals , Rats , Growth/physiology , Diabetes Complications , Insulin/pharmacology , Rats/classification
11.
Article in English | WPRIM | ID: wpr-36642

ABSTRACT

Hepatic steatosis is common in obese individuals with hyperinsulinemia and is an important hepatic manifestation of metabolic syndrome. Sterol regulatory binding protein-1c (SREBP-1c) is a master regulator of lipogenic gene expression in the liver. Hyperinsulinemia induces transcription of SREBP-1c via activation of liver X receptor (LXR) and specificity protein 1 (Sp1). Cilostazol is an antiplatelet agent that prevents atherosclerosis and decreases serum triglyceride levels. However, little is known about the effects of cilostazol on hepatic lipogenesis. Here, we examined the role of cilostazol in the regulation of SREBP-1c transcription in the liver. The effects of cilostazol on the expression of SREBP-1c and its target genes in response to insulin or an LXR agonist (T0901317) were examined using real-time RT-PCR and western blot analysis on cultured hepatocytes. To investigate the effect of cilostazol on SREBP-1c at the transcriptional level, transient transfection reporter assays and electrophoretic mobility shift assays (EMSAs) were performed. Cilostazol inhibited insulin-induced and LXR-agonist-induced expression of SREBP-1c and its downstream targets, acetyl-CoA carboxylase and fatty acid synthase, in cultured hepatocytes. Cilostazol also inhibited activation of the SREBP-1c promoter by insulin, T0901317 and Sp1 in a luciferase reporter assay. EMSA analysis showed that cilostazol inhibits SREBP-1c expression by repressing the binding of LXR and Sp1 to the promoter region. These results indicate that cilostazol inhibits insulin-induced hepatic SREBP-1c expression via the inhibition of LXR and Sp1 activity and that cilostazol is a negative regulator of hepatic lipogenesis.


Subject(s)
Animals , Cells, Cultured , Hep G2 Cells , Hepatocytes/drug effects , Humans , Hydrocarbons, Fluorinated/pharmacology , Insulin/pharmacology , Lipogenesis , Mice , Mice, Inbred C57BL , Orphan Nuclear Receptors/agonists , Promoter Regions, Genetic , Protein Binding , Rats , Sp1 Transcription Factor/metabolism , Sterol Regulatory Element Binding Protein 1/genetics , Sulfonamides/pharmacology , Tetrazoles/pharmacology
12.
Iranian Journal of Veterinary Research. 2012; 67 (4): 387-392
in Persian | IMEMR | ID: emr-154103

ABSTRACT

Improvement of sperm quality as a research field in reproductive biotechnology of domestic animal can be considered as a key element for in vitro fertilization. The aim of the present study was to investigate the effects of insulin and leptin on ovine sperm capacitation / acrosomal reaction, viability and fertilization. The semen samples of 10 Bakhtiari rams were collected by artificial vagina. Using dose response study, the most efficient doses of insulin and leptin were chosen. Each sample was assigned to four experimental groups including insulin [1nM], leptin [100nM], mixed of leptin-insulin and control [without hormone]. Sperm capacitation/acrosomal reaction, viability and fertilization were evaluated by chlortetracycline staining, eosin-negrosin and in-vitro fertilization methods, respectively. values were compared among groups by 1-way ANOVA. Values of capacitation/ acrosomal reaction rate showed significant increase in response to insulin and leptin at 30, 60 and 120 min time points. The sperm viability was significantly [p<0.05] increased in response to insulin when compared with the control group at 30 min time point, without any effect in the other time points. On the other hand, insulin and leptin did not show significant effect [p>0.05] on sperm fertilization. This study indicated that insulin and leptin improved ram sperm capacitation / acrosomal reaction and viability while their effects on in vitro embryo production were inconsiderable


Subject(s)
Animals , Leptin/pharmacology , Insulin/pharmacology , Fertilization in Vitro
13.
Article in English | WPRIM | ID: wpr-211721

ABSTRACT

Recent evidence has suggested that human skin fibroblasts may represent a novel source of therapeutic stem cells. In this study, we report a 3-stage method to induce the differentiation of skin fibroblasts into insulin-producing cells (IPCs). In stage 1, we establish the isolation, expansion and characterization of mesenchymal stem cells from human labia minora dermis-derived fibroblasts (hLMDFs) (stage 1: MSC expansion). hLMDFs express the typical mesenchymal stem cell marker proteins and can differentiate into adipocytes, osteoblasts, chondrocytes or muscle cells. In stage 2, DMEM/F12 serum-free medium with ITS mix (insulin, transferrin, and selenite) is used to induce differentiation of hLMDFs into endoderm-like cells, as determined by the expression of the endoderm markers Sox17, Foxa2, and PDX1 (stage 2: mesenchymal-endoderm transition). In stage 3, cells in the mesenchymal-endoderm transition stage are treated with nicotinamide in order to further differentiate into self-assembled, 3-dimensional islet cell-like clusters that express multiple genes related to pancreatic beta-cell development and function (stage 3: IPC). We also found that the transplantation of IPCs can normalize blood glucose levels and rescue glucose homeostasis in streptozotocin-induced diabetic mice. These results indicate that hLMDFs have the capacity to differentiate into functionally competent IPCs and represent a potential cell-based treatment for diabetes mellitus.


Subject(s)
Animals , Biomarkers/metabolism , Cell Culture Techniques , Cell Differentiation , Cell Proliferation/drug effects , Cell Separation , Cells, Cultured , Dermis/cytology , Diabetes Mellitus, Experimental/surgery , Female , Fibroblasts/cytology , Genitalia, Female/cytology , Glucose/metabolism , Hepatocyte Nuclear Factor 3-beta/metabolism , Homeodomain Proteins/metabolism , Humans , Insulin/pharmacology , Insulin-Secreting Cells/cytology , Islets of Langerhans Transplantation , Mesenchymal Stem Cells/cytology , Mice , Mice, Nude , Niacinamide/pharmacology , Recovery of Function , SOXF Transcription Factors/metabolism , Sodium Selenite/pharmacology , Trans-Activators/metabolism , Transferrin/pharmacology
14.
Article in English | WPRIM | ID: wpr-14960

ABSTRACT

Six transmembrane protein of prostate 2 (STAMP2) plays a key role in linking inflammatory and diet-derived signals to systemic metabolism. STAMP2 is induced by nutrients/feeding as well as by cytokines such as TNFalpha, IL-1beta, and IL-6. Here, we demonstrated that STAMP2 protein physically interacts with and decreases the stability of hepatitis B virus X protein (HBx), thereby counteracting HBx-induced hepatic lipid accumulation and insulin resistance. STAMP2 suppressed the HBx-mediated transcription of lipogenic and adipogenic genes. Furthermore, STAMP2 prevented HBx-induced degradation of IRS1 protein, which mediates hepatic insulin signaling, as well as restored insulin-mediated inhibition of gluconeogenic enzyme expression, which are gluconeogenic genes. We also demonstrated reciprocal expression of HBx and STAMP2 in HBx transgenic mice. These results suggest that hepatic STAMP2 antagonizes HBx-mediated hepatocyte dysfunction, thereby protecting hepatocytes from HBV gene expression.


Subject(s)
Animals , Female , Gene Expression , Gluconeogenesis/genetics , Hep G2 Cells , Humans , Insulin/pharmacology , Insulin Receptor Substrate Proteins/genetics , Insulin Resistance , Lipid Metabolism , Liver/metabolism , Male , Membrane Proteins/metabolism , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Transgenic , Oxidoreductases/metabolism , Phosphorylation , Protein Binding , Protein Processing, Post-Translational , Proteolysis , Receptor, Insulin/metabolism , Trans-Activators/physiology , Transcriptional Activation
15.
Säo Paulo med. j ; 129(6): 387-391, Dec. 2011. ilus, tab
Article in English | LILACS | ID: lil-611806

ABSTRACT

CONTEXT AND OBJECTIVE: Preeclampsia is a multi-systemic disease and one of the most frequent severe health problems during pregnancy. Binding of insulin triggers phosphorylation and activates cytoplasmic substrates such as phosphatidylinositol 3 kinase (PI3K). Phosphorylation of membrane phosphoinositide 2 (PIP2) to phosphoinositide 3 (PIP3) by PI3K starts Akt/PKB activation. Defects in phosphorylation of the insulin receptor and its substrates have an important role in insulin resistance. Studies have shown that insulin resistance is associated with preeclampsia and its pathophysiology. The aim here was to investigate insulin stimulation of the Akt/PKB pathway in the placenta, in normal and preeclampsia parturients. DESIGN AND SETTING: Cross-sectional study in a tertiary public university hospital. METHODS: Placentas were collected from 12 normal and 12 preeclampsia patients. These were stimulated and analyzed using Western blot to quantify the Akt/PKB phosphorylation. RESULTS: The insulin stimulation was confirmed through comparing the stimulated group (1.14 ± 0.10) with the non-stimulated group (0.91 ± 0.08; P < 0.001). The phosphorylation of Akt/PKB did not differ between the placenta of the normal patients (1.26 ± 0.16) and those of the preeclampsia patients (1.01 ± 0.11; P = 0.237). CONCLUSIONS: In vitro insulin stimulation of the human placenta has been well established. There was no difference in Akt/PKB phosphorylation, after stimulation with insulin, between placentas of normal and preeclampsia patients. Nevertheless, it cannot be ruled out that the Akt/PKB signaling pathway may have a role in the pathophysiology of preeclampsia, since the substrates of Akt/PKB still need to be investigated.


CONTEXTO E OBJETIVO: Pré-eclâmpsia (PE) é uma doença multissistêmica das mais frequentes e graves durante a gestação. A ligação da insulina inicia a fosforilação e ativação de substratos citoplasmáticos, tais como fosfatidil-inositol 3 quinase (PI3K). A fosforilação do fosfoinositol 2 (PIP2) da membrana em fosfoinosiltol 3 (PIP3) pela PI3K inicia a ativação da Akt/PKB. Defeitos na fosforilação do receptor de insulina e seus substratos têm papel importante na resistência à insulina. Estudos demonstraram que resistência à insulina está associada com pré-eclâmpsia e sua patofisiologia. O objetivo foi investigar a via de estimulação com insulina da Akt/PKB em placenta de parturientes normais e com pré-eclampsia. TIPO DE ESTUDO E LOCAL: Estudo do tipo transversal em um hospital universitário público de nível terciário. MÉTODOS: Vinte e quatro placentas (12 normais, 12 com PE) foram coletadas, estimuladas e analisadas por Western blot para quantificar a fosforilação da Akt/PKB. RESULTADOS: A estimulação com insulina foi confirmada comparando os grupos estimulados (1,14 ± 0,10) e não estimulados (0.91 ± 0.08; P < 0.001). A fosforilação de Akt/PKB não foi diferente na placenta de pacientes normais (1,26 ± 0,16) e com PE (1,01 ± 0,11; P = 0,237). CONCLUSÕES: A estimulação in vitro da placenta humana com insulina foi bem estabelecida. Não houve diferença na fosforilação da Akt/PKB após estimulação em placentas de pacientes normais e PE. Contudo, não é possível descartar a participação desta via de sinalização na patofisiologia da PE, uma vez que os substratos da Akt/PKB ainda precisam ser investigados.


Subject(s)
Adult , Female , Humans , Pregnancy , Insulin/pharmacology , Placenta/drug effects , Pre-Eclampsia/enzymology , Proto-Oncogene Proteins c-akt/metabolism , Blotting, Western , Case-Control Studies , Cross-Sectional Studies , Enzyme Activation , Insulin Resistance/physiology , Phosphorylation , Placenta/enzymology , Signal Transduction
16.
Acta cir. bras ; 26(5): 396-403, Sept.-Oct. 2011. graf, tab
Article in English | LILACS | ID: lil-599643

ABSTRACT

PURPOSE: To evaluate the effects of ischemic preconditioning (IPC) associate with different preservation solutions, in the protecting of gut. METHODS: Four groups of 14 rats underwent laparotomy and collecting 20 cm of ileum, for preservation, at 4ºC, in Belzer (Belz), Ringer (RL), Celsior (Cs) and Custodiol (Cust) solutions, for 24 hours. Prior to collection, half of the animals in each group were subjected to IPC. During preservation, in the periods of zero, 12, 18 and 24 hours, were conducted evaluating the degree of mucosal injury and dosage of malondialdehyde acid (MDA). RESULTS: In all periods the RL group, with and without IPC, presented MDA values higher than the Belz and Cs. The degree of mucosal injury in the non-ipc RLgroup with 12h preservation was higher than the others; with 18 and 24h, the RL and Cust had higher degrees of damage than Cs and Belz. With IPC, in all periods, the group Cs and Belz had lower degrees of injury. CONCLUSION: The Celsior and Belzer solutions had better protective effects on the gut and these effects were enhanced by IPC.


OBJETIVO: Avaliar os efeitos do precondicionamento isquêmico (PCI) associado a diferentes soluções de preservação, na proteção do intestino delgado. MÉTODOS: Quatro grupos de 14 ratos Wistar, foram submetidos à laparotomia e coleta de 20 cm de íleo, para preservação, a 4ºC, nas soluções de Belzer (Belz), Ringer (RL), Celsior (Cs) e Custodiol (Cust) por 24 horas. Previamente à coleta, em metade dos animais de cada grupo, o intestino foi submetido ao PCI. Durante a preservação, nos períodos de Zero, 12, 18 e 24 horas, foram realizados avaliação do grau de lesão da mucosa e dosagem do ácido malondialdeído (MDA). RESULTADOS: Em todos os períodos o grupo RL, sem e com pci, apresentou valores maiores de MDA do que o Belz e Cs. O grau de lesão da mucosa nos grupos sem pci com preservação de 12h, no grupo RL, foi maior que nos demais; com 18h e 24h o grupo RL e Cust apresentaram maiores graus de lesão do que Cs e Belz. Com o pci, em todos os períodos, os grupos Belz e Cs apresentaram menores graus de lesão CONCLUSÃO: As Soluções Celsior e Belzer tiveram melhores efeitos na proteção do intestino e estes efeitos foram incrementados pelo precondicionamento isquêmico.


Subject(s)
Animals , Male , Rats , Intestinal Mucosa , Ischemic Preconditioning , Intestine, Small/blood supply , Organ Preservation Solutions/pharmacology , Organ Preservation/methods , Adenosine/pharmacology , Allopurinol/pharmacology , Disaccharides/pharmacology , Electrolytes/pharmacology , Glucose/pharmacology , Glutamates/pharmacology , Glutathione/pharmacology , Histidine/pharmacology , Insulin/pharmacology , Isotonic Solutions/pharmacology , Malondialdehyde/analysis , Mannitol/pharmacology , Potassium Chloride/pharmacology , Procaine/pharmacology , Rats, Wistar , Raffinose/pharmacology , Time Factors
17.
Article in English | WPRIM | ID: wpr-131296

ABSTRACT

Cholesterol 7alpha-hydroxylase (CYP7A1) regulates the balance between cholesterol supply and metabolism by catalyzing the rate-limiting step of bile acid biosynthesis. The transcriptional activity of CYP7A1 is tightly controlled by various nuclear receptors. A forkhead transcription factor O1 (FOXO1) plays a critical role in metabolism, and insulin inactivates FOXO1 through Akt-dependent phosphorylation and nuclear exclusion. We investigated the role of insulin-Akt-FOXO1 signaling pathway in CYP7A1 transcriptional regulation since we found putative insulin-response elements, FOXO1 binding sequences, in both rat and human CYP7A1 promoters. However, ectopic expression of FOXO1 increased the rat CYP7A1-, but mildly reduced human CYP7A1-promoter activities in a dose-dependent manner. Similarly to bile acids, insulin treatment increased small heterodimer partner (SHP) mRNA rapidly and transiently, leading to the suppression of CYP7A1 transcription in both human and rodents. Chromatin immunoprecipitation showed that FOXO1 directly bound to rat CYP1A1 promoter in the absence of insulin. FOXO1 binding to the rat promoter was diminished by insulin treatment as well as by expression of SHP. Our results suggest that the stimulation of insulin- signaling pathway of Akt-FOXO1 and SHP expression may regulate cholesterol/bile acid metabolisms in liver, linking carbohydrate and cholesterol metabolic pathways. A prolonged exposure of insulin in hyperinsulinemic insulin resistance or diabetic status represses CYP7A1 transcription and bile acid biosynthesis through SHP induction and FOXO1 inactivation, leading to impairment of the hepatic cholesterol/bile acid metabolisms.


Subject(s)
Animals , Bile Acids and Salts/metabolism , Cholesterol/metabolism , Cholesterol 7-alpha-Hydroxylase/genetics , Forkhead Transcription Factors/genetics , Gene Expression Regulation/drug effects , Glucose/metabolism , Hep G2 Cells , Humans , Insulin/pharmacology , Lipid Metabolism/drug effects , Liver/metabolism , Mice , Mice, Inbred C57BL , Mutagenesis, Site-Directed , Nerve Tissue Proteins/genetics , Protein Binding/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Rats , Receptors, Cytoplasmic and Nuclear/genetics , Sequence Deletion/genetics , Signal Transduction/drug effects , Transcriptional Activation/drug effects
18.
Article in English | WPRIM | ID: wpr-131293

ABSTRACT

Cholesterol 7alpha-hydroxylase (CYP7A1) regulates the balance between cholesterol supply and metabolism by catalyzing the rate-limiting step of bile acid biosynthesis. The transcriptional activity of CYP7A1 is tightly controlled by various nuclear receptors. A forkhead transcription factor O1 (FOXO1) plays a critical role in metabolism, and insulin inactivates FOXO1 through Akt-dependent phosphorylation and nuclear exclusion. We investigated the role of insulin-Akt-FOXO1 signaling pathway in CYP7A1 transcriptional regulation since we found putative insulin-response elements, FOXO1 binding sequences, in both rat and human CYP7A1 promoters. However, ectopic expression of FOXO1 increased the rat CYP7A1-, but mildly reduced human CYP7A1-promoter activities in a dose-dependent manner. Similarly to bile acids, insulin treatment increased small heterodimer partner (SHP) mRNA rapidly and transiently, leading to the suppression of CYP7A1 transcription in both human and rodents. Chromatin immunoprecipitation showed that FOXO1 directly bound to rat CYP1A1 promoter in the absence of insulin. FOXO1 binding to the rat promoter was diminished by insulin treatment as well as by expression of SHP. Our results suggest that the stimulation of insulin- signaling pathway of Akt-FOXO1 and SHP expression may regulate cholesterol/bile acid metabolisms in liver, linking carbohydrate and cholesterol metabolic pathways. A prolonged exposure of insulin in hyperinsulinemic insulin resistance or diabetic status represses CYP7A1 transcription and bile acid biosynthesis through SHP induction and FOXO1 inactivation, leading to impairment of the hepatic cholesterol/bile acid metabolisms.


Subject(s)
Animals , Bile Acids and Salts/metabolism , Cholesterol/metabolism , Cholesterol 7-alpha-Hydroxylase/genetics , Forkhead Transcription Factors/genetics , Gene Expression Regulation/drug effects , Glucose/metabolism , Hep G2 Cells , Humans , Insulin/pharmacology , Lipid Metabolism/drug effects , Liver/metabolism , Mice , Mice, Inbred C57BL , Mutagenesis, Site-Directed , Nerve Tissue Proteins/genetics , Protein Binding/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Rats , Receptors, Cytoplasmic and Nuclear/genetics , Sequence Deletion/genetics , Signal Transduction/drug effects , Transcriptional Activation/drug effects
19.
Clinics ; 65(11): 1139-1142, 2010. tab
Article in English | LILACS | ID: lil-571431

ABSTRACT

INTRODUCTION: Endothelium-dependent dilation is improved in insulin-treated diabetic patients, but this effect is probably due to improved glycemic control. The objective of the present study was to compare endothelium-dependent dilation in patients with well-controlled type 2 diabetes who are or are not using insulin as part of their therapy. METHODS: We studied 27 patients with type 2 diabetes (11 women, 60.3 years ± 6 years, with HbA1c < 7 percent and no nephropathy), including 16 patients treated with anti-diabetic agents (No-Ins, 8 women) and 11 patients treated with insulin alone or in combination with anti-diabetic agents (Ins, 3 women). Endothelial function was evaluated by the dorsal hand vein technique, which measures changes in vein diameter in response to phenylephrine, acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation). RESULTS: Age, systolic blood pressure (No-Ins: 129.4 mmHg ± 11.8 mmHg, Ins: 134.8 mmHg ± 12.0 mmHg; P= 0.257), HbA1c, lipids and urinary albumin excretion rate [No-Ins: 9 mg/24 h (0-14.1 mg/24 h) vs. Ins: 10.6 mg/24 h (7.5-14.4 mg/24 h), P=0.398] were similar between groups. There was no difference between endothelium-dependent vasodilation of the No-Ins group (59.3 percent ± 26.5 percent) vs. the Ins group (54.0 percent ± 16.3 percent; P=0.526). Endothelium-independent vasodilation was also similar between the No-Ins (113.7 percent ± 35.3 percent) and Ins groups (111.9 percent ± 28.5 percent; P=0.888). CONCLUSIONS: Subcutaneous insulin therapy does not interfere with venous endothelial function in type 2 diabetes when glycemic and blood pressure control are stable.


Subject(s)
Aged , Female , Humans , Male , Middle Aged , /drug therapy , Endothelium, Vascular/drug effects , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Vasodilation/drug effects , Blood Pressure/drug effects , /physiopathology , Endothelium, Vascular/physiology , Risk Factors , Statistics, Nonparametric
20.
Article in English | WPRIM | ID: wpr-203592

ABSTRACT

Chronic and heavy alcohol consumption is one of the causes of heart diseases. However, the effects of ethanol on insulin sensitivity in myocardium has been unclear. To investigate the effects of ethanol on the expression of AMP-activated protein kinase (AMPK), myocyte enhancer factor 2 (MEF2) and glucose transporter 4 (GLUT4), all of which are involved in the regulation of insulin sensitivity, in the myocardium, we performed three parts of experiments in vivo and in vitro. I: Rats were injected with 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR, 0.8 mg.kg(-1)) for 2 h. II: Rats received different dose (0.5, 2.5 or 5 g.kg(-1).d(-1)) of ethanol for 22-week. III: Primary neonatal rat cardiomyocytes were isolated and treated with or without 100 mM ethanol or 1 mM AICAR for 4 h. The cardiac protein and mRNA expression of AMPKalpha subunits, MEF2 and GLUT4 were observed by western-blotting and RT-PCR, respectively. Serum TNFalpha levels were assessed by ELISA. The results showed chronic ethanol exposure induced insulin resistance. Ethanol decreased the mRNA levels of AMPKalpha1 and alpha2, the protein levels of total- and phospho-AMPKalpha in cardiomyocytes. Similarly, ethanol showed inhibitory effects on both the mRNA and protein levels of MEF2A and 2D, and GLUT4 in a dose-response-like fashion. Correlation analysis implied an association between phospho-AMPKalpha and MEF2A or MEF2D, and between the levels of MEF2 protein and GLUT4 transcription. In addition, ethanol elevated serum TNFalpha level. Taken together, chronic ethanol exposure decreases the expression of AMPKalpha and MEF2, and is associated with GLUT4 decline in rat myocardium.


Subject(s)
AMP-Activated Protein Kinases/genetics , Aminoimidazole Carboxamide/analogs & derivatives , Animals , Enzyme Activation/drug effects , Ethanol/administration & dosage , Feeding Behavior/drug effects , Gene Expression Regulation/drug effects , Glucose Transporter Type 4/genetics , Insulin/pharmacology , Insulin Resistance , Male , Myocardium/enzymology , Myogenic Regulatory Factors/antagonists & inhibitors , Protein Isoforms/antagonists & inhibitors , RNA, Messenger/genetics , Rats , Rats, Wistar , Ribonucleotides/pharmacology , Time Factors , Tumor Necrosis Factor-alpha/blood
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