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2.
Rev. Soc. Bras. Clín. Méd ; 13(2)jun. 2015. tab
Article in Portuguese | LILACS | ID: lil-749182

ABSTRACT

BACKGROUND: The Polycystic Ovary Syndrome (PCOS) is the most common endocrinopathy and one of the main causes of infertility in women. OBJECTIVES: This study aimed to evaluate the correlation between clinical hyperandrogenism assessed by modified Ferriman-Gallwey (F-G) score and metabolic parameters in Polycystic Ovary Syndrome women. METHODS: This observational study included fifty Polycystic Ovary Syndrome subjects. Detailed information about body mass index (BMI) and abdominal circumference (AC) were obtained from each subject. F-G score was applied to assess hirsutism through visual method. Serum levels of insulin, glucose and testosterone were measured. RESULTS: A positive correlation was observed between F-G score with body mass index, abdominal circumference and insulin. CONCLUSIONS: Obesity, mainly abdominal adipose tissue, and insulin levels correlate with hyperandrogenism in Polycystic Ovary Syndrome women, analyzed by F-G score. F-G score could be a marker to evaluate metabolic disorders in Polycystic Ovary Syndrome women.


JUSTIFICATIVA: A Síndrome dos Ovários Policísticos (SOP) é a endocrinopatia mais comum e uma das principais causas de infertilidade em mulheres. OBJETIVOS: O presente estudo teve como objetivo avaliar a correlação entre hiperandrogenismo clínico, avaliado pela escala de Ferriman-Gallwey (FG) modificada e parâmetros metabólicos em mulheres com a Síndrome dos Ovários Policísticos. MÉTODOS: Este estudo observacional incluiu cinquenta mulheres com Síndrome dos Ovários Policísticos. Informações detalhadas sobre o índice de massa corporal (IMC) e circunferência abdominal (CA) foram obtidas de cada participante. A escala FG foi aplicada para avaliar o hirsutismo através do método visual. Níveis séricos de insulina, glicose e testosterona foram também avaliados. RESULTADOS: Observou-se uma correlação positiva entre a escala FG e o índice de massa corporal, circunferência abdominal e insulina. CONCLUSÕES: A obesidade, principalmente o tecido adiposo abdominal, e os níveis de insulina se correlacionam com hiperandrogenismo em mulheres com Síndrome dos Ovários Policísticos, analisados por meio da escala FG. Desta forma, esta escala poderia ser um marcador para avaliar distúrbios metabólicos em mulheres com Síndrome dos Ovários Policísticos.


Subject(s)
Humans , Female , Adult , Insulin/physiology , Obesity/complications , Polycystic Ovary Syndrome/complications , Hyperandrogenism/metabolism , Hirsutism/metabolism , Observational Study
3.
Article in English | WPRIM | ID: wpr-191852

ABSTRACT

The present study was conducted to investigate the effects of resveratrol on the insulin signaling pathway in the liver of obese mice. To accomplish this, we administered resveratrol to high fat diet-induced obese mice and examined the levels of protein phosphorylation in the liver using an antibody array. The phosphorylation levels of 10 proteins were decreased in the high fat diet and resveratrol (HFR) fed group relative to the levels in the high fat diet (HF) fed group. In contrast, the phosphorylation levels of more than 20 proteins were increased in the HFR group when compared with the levels of proteins in the HF group. Specifically, the phosphorylation levels of Akt (The308, Tyr326, Ser473) were restored to normal by resveratrol when compared with the levels in the HF group. In addition, the phosphorylation levels of IRS-1 (Ser636/Ser639), PI-3K p85-subunit alpha/gamma(Tyr467/Tyr199), PDK1 (Ser241), GSK-3alpha (S21) and GSK-3 (Ser9), which are involved in the insulin signaling pathway, were decreased in the HF group, whereas the levels were restored to normal in the HFR group. Overall, the results show that resveratrol restores the phosphorylation levels of proteins involved in the insulin signaling pathway, which were decreased by a high fat diet.


Subject(s)
Animals , Anti-Inflammatory Agents/pharmacology , Fluorescent Antibody Technique , Insulin/physiology , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Phosphorylation , Proteins/metabolism , Signal Transduction/drug effects , Stilbenes/pharmacology
4.
São Paulo; s.n; s.n; 2013. 112 p. tab, graf, ilus.
Thesis in Portuguese | LILACS | ID: biblio-846936

ABSTRACT

Fontes alternativas de células ß têm sido estudadas para o tratamento de Diabetes mellitus tipo 1, dentre as quais a mais promissora consiste das células-tronco diferenciadas em células produtoras de insulina (IPCs). Alguns trabalhos demonstram a capacidade de células-tronco embrionárias murinas (mESCs) de formarem estruturas semelhantes a ilhotas pancreáticas, porém, os níveis de produção de insulina são insuficientes para a reversão do diabetes em camundongos diabetizados. Este trabalho visa desenvolver um protocolo adequado para geração de IPCs e contribuir para a identificação e caracterização funcional de novos genes associados à organogênese pancreática. Logo no início da diferenciação das mESCs em IPCs, foi possível verificar o surgimento de células progenitoras, evidenciado pela expressão de marcadores importantes da diferenciação beta-pancreática. Ao final do processo de diferenciação in vitro, ocorreu a formação de agrupamentos (clusters) semelhantes a ilhotas, corando positivamente por ditizona, que é específica para células ß-pancreáticas. Para avaliar seu potencial in vivo, estes clusters foram microencapsulados em Biodritina® e transplantados em camundongos diabetizados. Apesar dos níveis de insulina produzidos não serem suficientes para estabelecer a normoglicemia, os animais tratados com IPCs apresentaram melhores condições, quando comparados ao grupo controle, tendo melhor controle glicêmico, ganho de massa corpórea e melhor aparência da pelagem, na ausência de apatia. Além disso, análise dos clusters transplantados nestes animais indicou aumento da expressão de genes relacionados à maturação das células ß. Porém, quando estes clusters foram microencapsuladas em Bioprotect® e submetidos à maturação in vivo em animais normais, ocorreu um aumento drástico na expressão de todos os genes analisados, indicando sua maturação completa em células beta. O transplante destas células completamente maturadas em animais diabetizados, tornou-os normoglicêmicos e capazes de responder ao teste de tolerância à glicose (OGTT) de forma semelhante aos animais normais. A segunda parte do trabalho visou analisar genes diferencialmente expressos identificados em estudo anterior do nosso grupo, comparando, através de DNA microarray, mESCs indiferenciadas e diferenciadas em IPCs. Um dos genes diferencialmente expressos é aquele que codifica para a Purkinge cell protein 4 (Pcp4), sendo 3.700 vezes mais expresso em IPCs. Para investigar o possível papel do gene Pcp4 em células ß e no processo de diferenciação ß-pancreática, adotou-se o enfoque de genômica funcional, superexpressando e inibindo sua expressão em células MIN-6 e mESCs. Apesar da alteração na expressão de Pcp4 em células MIN-6 não ter interferido de forma expressiva na expressão dos genes analisados, quando inibido, modificou o perfil da curva de crescimento celular, aumentando seu tempo de dobramento de forma significativa e diminuindo da viabilidade celular em ensaios de indução de apoptose. Já na diferenciação de mESCs em IPCs, a superexpressão de Pcp4 interferiu de forma positiva apresentando uma tendência a aumentar a expressão dos genes relacionado à diferenciaçãoß-pancreática. Concluindo, desenvolvemos um novo protocolo de diferenciação de mESCs em IPCs as quais foram capazes de reverter o diabetes em camundongos diabetizados e descrevemos, pela primeira vez, o gene Pcp4 como sendo expresso em células ß-pancreáticas, podendo estar relacionado à manutenção da viabilidade celular e maturação destas células


New cellular sources for type 1 Diabetes mellitus treatment have been previously investigated, the most promising of which seems to be the insulin producing cells (IPCs), obtained by stem cells differentiation. Some reports show that murine embryonic stem cells (mESCs) are able to form islet-like structures, however, their insulin production is insufficient to render diabetic mice normoglycemic. This work aims at developing an adequate protocol for generation of IPCs and searching for new genes which could be involved in the pancreatic organogenesis process. Early on during mESCs differentiation into IPCs, we observed the presence of progenitor cells, which were able to express pancreatic ß-cell markers. At the end of the differentiation process, the islet-like clusters positively stained for the insulin-specific dithizone. These clusters were microencapsulated in Biodritin® microcapsules, and then transplanted into diabetized mice. Although the levels of insulin production were insufficient for the animals to achieve normoglycemia, those which received IPCs displayed improved conditions, when compared to the control group, as judged by a better glycemic control, body weight gain and healthy fur appearance, in the absence of apathy. In addition, when these transplantated clusters were retrieved, high levels of expression of the genes related to ß-cell maturation were detected. IPCs were also microencapsulated in Bioprotect® and subjected to in vivo maturation in normal animals. A dramatic increase of the analyzed genes expression was observed, indicating complete maturation of the differentiated cells. When these cells were transplanted into diabetized mice, these animals achieved normoglycemia and were able to display glucose tolerance test (OGTT) response very similar to that of normal mice. In the second part of this work, we analyzed upregulated genes described in previous work from our group, comparing undifferentiated mESCs to IPCs using a microarray platform. One of these genes is that coding for the Purkinje cell protein 4 (Pcp4), which is 3,700 more expressed than in undifferentiated mESC cells. We adopted a functional genomics approach to investigate the role played by the Pcp4 gene in ß-cells and in ß-cell differentiation, by inducing overexpression and knocking down this gene in MIN-6 and mESC cells. Although the differential expression of Pcp4 in MIN-6 was not able to interfere with the expression of the genes analyzed, we observed different cell growth rates, with increased doubling time and decreased cell viability when its expression was knocked down. In addition, overexpression of Pcp4 in mESCs subjected to differentiation into IPCs apparently increases the expression of genes related to ß-cell differentiation. In conclusion, we developed a new protocol for ESCs differentiation into IPCs, which is able to revert diabetes in diabetized mice, and we also describe here, for the first time, the Pcp4 gene as being expressed in pancreatic ß-cells and possibly being related to maintenance of cell viability and ß-cell maturation


Subject(s)
Mice , Genes , Insulin/physiology , Diabetes Mellitus, Type 1/prevention & control , Embryonic Stem Cells/classification , Gene Expression , Islets of Langerhans , Molecular Biology , Mouse Embryonic Stem Cells/metabolism , Organogenesis , Pancreas , Purkinje Cells/classification
5.
Article in English | IMSEAR | ID: sea-145783

ABSTRACT

Background: The gingiva has been shown to be a target tissue for several hormones. Insulin induces uptake of glucose in the peripheral tissues by upregulating the Glucose transporter 4 expression. Little information is available on the expression of Glucose transporter 4 in human gingiva. Aim: In this regard, a pilot study was performed with the aim of determining the distribution pattern of Glucose transporter 4 in healthy human gingiva. Materials and Methods: Immuno-histochemistry was performed on 10 mounted sections of healthy human gingiva with the primary antibody Glucose Transporter 4 (GLUT 4). Appropriate positive and negative controls were used. Results: Glucose transporter 4 expression was observed in the basal and suprabasal layers of the gingival epithelium and fibroblasts of the gingival connective tissue. Conclusion: This may be the first study to demonstrate the expression of GLUT 4 in the healthy human gingiva. The results of this study raise the possibility that gingiva may serve as a target tissue for insulin action.


Subject(s)
Gingiva/analysis , Glucose/physiology , Glucose Transporter Type 4/immunology , Glucose Transporter Type 4/isolation & purification , Humans , Immunohistochemistry , Insulin/physiology
6.
Article in English | WPRIM | ID: wpr-149762

ABSTRACT

This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve beta-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients.


Subject(s)
Adipokines/blood , Animals , Blood Glucose , Diabetes Mellitus, Type 2/drug therapy , Dietary Supplements , Dyslipidemias/blood , Glucose Tolerance Test , Hyperglycemia/blood , Hypoglycemic Agents/administration & dosage , Hypolipidemic Agents/administration & dosage , Insulin/physiology , Insulin Resistance , Insulin-Secreting Cells/physiology , Leptin/blood , Lipid Metabolism/drug effects , Lipids/blood , Male , Organ Specificity , Rats , Rats, Long-Evans , Taurine/administration & dosage
7.
Diagnóstico (Perú) ; 49(4): 180-185, oct.-dic. 2010.
Article in Spanish | LILACS, LIPECS | ID: lil-590811

ABSTRACT

La diabetes, el sobrepeso y la obesidad son enfermedades crónicas no transmisibles que se incrementan paulatinamente por desórdenes alimenticios, disminución de la actividad física y trastornos endocrinológicos. La insulina además de regular el metabolismo de la glucosa es un neuromodulador del sistema nervioso central, interviniendo en los procesos de funcionamiento neuronal y sus alteraciones afectan el desempeño cognitivo. Diversas patologías como el síndrome de resistencia a la insulina, hiperinsulinemia y la diabetes incrementan la respuesta inflamatoria sistémica y el estrés oxidativo. En el presente artículo revisamos la fisiopatología de la insulina y el deterioro cognitivo, sus péptidos relacionados y el rol que tiene la dieta y las enfermedades asociadas.


Diabetes, overweight and obesity are chronic non communicable diseases that are increased gradually by eating disorders, decreased physical activity and endocrinological disorders. Insulin besides regulate glucose is a neuromodulator of the central nervous system is involved in processes of neuronal function and its alterations affect cognitive performance. Pathologies such as the syndrome of insulin resistance, hyperinsulinemia and diabetes increase the systemic inflammatory response and oxidative stress. This paper reviews the pathophysiology of insulin and cognitive decline, related peptides and role of diet and associated diseases.


Subject(s)
Humans , Male , Female , Diabetes Mellitus , Alzheimer Disease , Insulin/physiology , Insulin/therapeutic use , Obesity , Pathology , Insulin Resistance , Epidemiologic Studies
8.
Rev. chil. endocrinol. diabetes ; 2(4): 223-227, oct. 2009.
Article in Spanish | LILACS | ID: lil-610277

ABSTRACT

Insulin resistance appears in several pathological conditions but unfortunately a simple, low cost, reproducible and easy to perform method to measure it isstill lacking. This method should resemble as closely as possible the physiological response to insulin and should be able to evaluate the sensitivity to the hormone of different tissues and systems. We herein analyze the factors that modify basal insulin determinations and the different methods available to measure insulin resistance.


Subject(s)
Humans , Glucose Tolerance Test , Insulin Resistance , Insulin/physiology , Insulin/blood
9.
Int. braz. j. urol ; 33(3): 407-413, May-June 2007. ilus
Article in English | LILACS | ID: lil-459864

ABSTRACT

PURPOSE: The role of insulin 3-like (Insl3) hormone signaling in the testicular descent process has been demonstrated. The purpose of the present study was to evaluate epididymal development in Insl3-deficient mice. MATERIALS AND METHODS: Heterozygous and homozygous Insl3 mutants of a mixed CD1 X 129/Sv genetic background were generated by breeding Insl3-/- females with Insl3+/- males, and their genotypes were determined by polymerase chain reaction. On the first postnatal day, newborn males were sacrificed, embedded in paraffin, and cut in 4 µm sections. Sections were stained with hematoxylin/eosin and immunoreacted with anti-± actin antibody. RESULTS: An analysis of stained sections indicated an arrest in the development of the epididymis in all homozygous mice. The cauda and corpus of the epididymis were undersized. Compared to the heterozygous epididymis, the homozygous epididymis had fewer peritubular layers and dwarfish musculature. We confirmed this with immunostaining with monoclonal antibodies against ± -smooth muscle actin. CONCLUSION: Defective development of the smooth musculature in the epididymis of Insl3 homozygous mutant mice, combined with its high intraabdominal undescended position, supports previous observations regarding the importance of intact epididymis morphology and function for descent of the epididymo-testicular unit.


Subject(s)
Animals , Female , Male , Mice , Epididymis/growth & development , Insulin/deficiency , Testis/growth & development , Homozygote , Immunohistochemistry , Insulin/genetics , Insulin/physiology , Mice, Mutant Strains , Proteins/genetics , Proteins/physiology , Testis/physiology
10.
Arq. bras. endocrinol. metab ; 51(3): 431-436, abr. 2007. ilus, graf
Article in Portuguese | LILACS | ID: lil-452184

ABSTRACT

OBJETIVOS: Avaliar a morfologia das organelas e do citoesqueleto em células pancreáticas humanas cultivadas e a mobilização de Ca2+ em resposta à glicose e ACh por medidas fluorimétricas. MATERIAL E MÉTODOS: As células foram semeadas em lamínulas, fixadas e marcadas com uma combinação de fluoróforos: o núcleo foi corado com DAPI e as mitocôndrias, com Mytotracker Red. Foram utilizados faloidina e anticorpos secundários conjugados com Alexa Fluor verde e vermelho fluorescentes (488 e 594) para identificar proteína actina F e receptor muscarínico tipo M3, respectivamente. Para estudar a mobilização de Ca2+, as células foram incubadas com fura-2/AM. RESULTADOS: As células pancreáticas humanas apresentaram morfologia preservada com grande quantidade de mitocôndrias. Na região de maior densidade celular, evidenciou-se as pseudo-ilhotas e os receptores muscarínicos M3. Por meio da elevação da [Ca2+]c, devido à ação da glicose e ACh, mostrou-se preservação da capacidade responsiva a esses estímulos e foi dependente de concentração desses agonistas. A glicose promoveu uma resposta sustentada e a ACh induziu uma resposta bifásica. CONCLUSÃO: As células pancreáticas humanas cultivadas conservaram sua morfologia. A mobilização de Ca2+ em resposta à glicose e a ACh confirma a sua funcionalidade. Os receptores muscarínicos M3 estão presentes nessas células.


AIMS: The proposal of this study was to analyze morphology of the organelles and cytoskeleton in human pancreatic cells cultured and the mobilization of the cytosolic calcium ([Ca2+]c) in response to glucose and ACh by fluorimetry method. MATERIAL AND METHODS: The cells were plated on glass coverslips, fixed and stained with a combination of fluorophores: the nuclei were stained with DAPI and mitochondria with Mytotracker Red. It was used phalloidin and the secondary antibodies Alexa Fluor conjugated green and red-fluorescent (488 and 594) to identify the protein cell actin F and type M3 muscarinic receptor respectively. The cells also were loaded with fura-2/AM to study Ca2+ mobilization. RESULTS: The human pancreatic cells show characteristics morphologically preserved with great amount of mitochondria. In region major cell density was evidenced pseudo-islets and type M3 muscarinic receptors. Through increase of [Ca2+]c due to action of glucose and ACh were shown that the cellsÆ capacity to respond to these stimuli were conserved. The elevation of the [Ca2+]c depended on concentration by glucose-induced promoting sustained phase and ACh-induced a biphasic response. CONCLUSION: The morphologic characteristics of human pancreatic cells cultured were preserved. The Ca2+ mobilization in response to glucose and ACh confirmed its functionality. The expression of the M3 muscarinic receptors in human pancreatic cell cultured was demonstrated.


Subject(s)
Humans , Acetylcholine/pharmacology , Calcium Signaling/physiology , Glucose/pharmacology , Insulin/physiology , Islets of Langerhans/drug effects , Analysis of Variance , Cell Nucleus Shape , Cells, Cultured , Cell Culture Techniques/methods , Cholinergic Agonists/pharmacology , Immunohistochemistry , Insulin-Secreting Cells/physiology , Insulin/biosynthesis , Insulin , Islets of Langerhans/chemistry , Islets of Langerhans/cytology , Islets of Langerhans/ultrastructure , Organelles/chemistry , /chemistry , /metabolism
11.
Arq. bras. endocrinol. metab ; 51(2): 195-203, mar. 2007. ilus
Article in Portuguese | LILACS | ID: lil-449573

ABSTRACT

Insulina (Ins) e Angiotensina II (AII) são fundamentais no controle de dois sistemas vitais e inter-relacionados: o metabólico e o cardiocirculatório, respectivamente. A disfunção de qualquer um desses hormônios pode levar ao desenvolvimento de duas doenças de alta prevalência, muitas vezes concomitantes e, talvez, com fisiopatologia integrada - diabetes mellitus (DM) e hipertensão arterial (HA). Vários estudos mostram que os sistemas de sinalização intracelular de Ins e AII estão conectados e influenciam um ao outro. Esta comunicação molecular ocorre em diferentes etapas da sinalização celular e é importante para vários fenômenos fisiológicos, desde o desenvolvimento de hipertrofia cardíaca e aquisição de energia pelo coração, até a ação de drogas anti-hipertensivas. No nível extracelular, a enzima de conversão de angiotensina regula a síntese de AII e o acúmulo de bradicinina, e ambos desempenham papel regulador sobre a sinalização de Ins. No nível intracelular, a interação dos sinais de Ins e AII ocorre em dois momentos distintos. Inicialmente, em etapas mais precoces da sinalização celular, a AII, atuando através da cascata JAK-2/IRS-1/PI3-quinase, JNK e ERK, provoca a fosforilação em serina e a conseqüente inibição de elementos-chave da via de sinalização da Ins. Finalmente, a AII induz a expressão da proteína regulatória SOCS-3, que impõe um controle mais tardio sobre o sinal de Ins. Esta revisão discute os avanços mais recentes neste campo e a importância dessa interação molecular na fisiopatologia e na associação clínica de DM e HA.


Insulin (Ins) and angiotensin II (AII) play pivotal roles in the control of two vital and closely related systems: the metabolic and the circulatory, respectively. A failure in the proper action of each of these hormones results, to a variable degree, in the development of two highly prevalent and commonly overlapping diseases - diabetes mellitus (DM) and hypertension (AH). In recent years, a series of studies has revealed a tight connection between the signal transduction pathways that mediate Ins and AII actions in target tissues. This molecular cross-talk occurs at multiple levels and plays an important role in phenomena that range from the action of anti-hypertensive drugs to cardiac hypertrophy and energy acquisition by the heart. At the extracellular level, the angiotensin-converting enzyme controls AII synthesis but also interferes with Ins signaling through the proper regulation of AII and the accumulation of bradykinin. At an early intracellular level, AII, acting through JAK-2/IRS-1/PI3-kinase, JNK and ERK, may induce the serine phosphorylation and inhibition of key elements of the Ins-signaling pathway. Finally, by inducing the expression of the regulatory protein SOCS-3, AII may impose a late control on the Ins signal. This review will focus on the main advances obtained in this field and will discuss the implications of this molecular cross-talk in the common clinical association between DM and AH.


Subject(s)
Animals , Humans , Angiotensin II/physiology , Diabetes Mellitus/physiopathology , Hypertension/physiopathology , Insulin Resistance/physiology , Insulin/physiology , Signal Transduction/physiology , MAP Kinase Signaling System/physiology , Suppressor of Cytokine Signaling Proteins/physiology
12.
Article in English | IMSEAR | ID: sea-16528

ABSTRACT

Following the discovery of insulin 85 yr ago and the realization thereafter that in some individuals, tissues lose their responsiveness to this hormone, an enormous world-wide effort began to dissect the cellular mechanisms of insulin action and define abnormalities in the insulin-resistant state. A clear goal through the years has been to unravel the insulin signal transduction network regulating glucose transport. This line of investigation has provided tremendous insight into the physiology and pathophysiology surrounding the cellular processes controlled by insulin. Between the plasma membrane insulin receptor and the intracellularly sequestered insulin-responsive glucose transporter GLUT4, many events participate in the transduction of the insulin signal. In this review, we detail our current state of knowledge on the intricate insulin signaling network responsible for glucose transport in peripheral adipose and skeletal muscle tissues. In particular, we identify signaling connections spanning the insulin receptor and GLUT4. In addition, we discuss cytoskeletal mechanics and membrane docking and fusion mechanisms pertinently involved in the cellular redistribution of GLUT4 to the plasma membrane. On the whole, this review highlights the considerable progress in our understanding of insulin signaling in health and disease as we rapidly approach the centennial anniversary of insulin's discovery.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Glucose Transporter Type 4/physiology , Humans , Insulin/physiology , Insulin Resistance/physiology , Models, Biological , Obesity/physiopathology , Reference Values , Signal Transduction
13.
Article in English | WPRIM | ID: wpr-195954

ABSTRACT

It is well known that exercise can have beneficial effects on insulin resistance by activation of glucose transporter. Following up our previous report that caveolin-1 plays an important role in glucose uptake in L6 skeletal muscle cells, we examined whether exercise alters the expression of caveolin-1, and whether exercise-caused changes are muscle fiber and exercise type specific. Fifity week-old Sprague Dawley (SD) rats were trained to climb a ladder and treadmill for 8 weeks and their soleus muscles (SOL) and extensor digitorum longus muscles (EDL) were removed after the last bout of exercise and compared with those from non-exercised animals. We found that the expression of insulin related proteins and caveolins did not change in SOL muscles after exercise. However, in EDL muscles, the expression of insulin receptor beta (IRbeta) and glucose transporter-4 (GLUT-4) as well as phosphorylation of AKT and AMPK increased with resistance exercise but not with aerobic exercise. Also, caveolin-1 and caveolin-3 increased along with insulin related proteins only in EDL muscles by resistance exercise. These results suggest that upregulation of caveolin-1 in the skeletal muscle is fiber specific and exercise type specific, implicating the requirement of the specific mode of exercise to improve insulin sensitivity.


Subject(s)
AMP-Activated Protein Kinases , Animals , Caveolin 1/biosynthesis , Caveolin 3/metabolism , Female , Glucose Transporter Type 4/biosynthesis , Insulin/physiology , Multienzyme Complexes/metabolism , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/metabolism , Phosphorylation , Physical Conditioning, Animal , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Insulin/biosynthesis , Up-Regulation
14.
Acta Med Indones ; 2006 Jan-Mar; 38(1): 42-50
Article in English | IMSEAR | ID: sea-47194

ABSTRACT

Obesity has become a worldwide public health problem affecting millions of people. This is a chronic, stigmatized, and costly disease, rarely curable and is increasing in prevalence to a point today where we define obesity as an epidemic disease that not only in developed but also on developing countries. The pathogenesis of obesity is largely unknown, especially about energy regulatory mechanism that involved wide area of neuroendocrinology that is very interesting but very complex and makes internists "refuse" to learn. Obesity occurs through a longstanding imbalance between energy intake and energy expenditure, influenced by a complex biologic system that regulates appetite and adiposity. Obesity influences the pathogenesis of hypertension, type 2 diabetes, dyslipidemia, kidney, heart, and cerebrovascular disease. It is very wise for every internist to learn the pathogenesis and treatment of this worldwide diseases. Until now, the available treatments, including drugs, are palliative and are effective only while the treatment is being actively used; and besides so many side effects reported.


Subject(s)
Appetite Depressants/therapeutic use , Energy Metabolism , Ghrelin , Homeostasis , Humans , Hypothalamus/physiology , Insulin/physiology , Leptin/physiology , Obesity/drug therapy , Peptide Hormones/physiology , Sympathetic Nervous System/physiology
15.
J Indian Med Assoc ; 2005 Nov; 103(11): 594-5, 599
Article in English | IMSEAR | ID: sea-105612

ABSTRACT

Type 2 diabetic patients pass through a phase of impaired glucose tolerence and/or impaired fasting glucose known as 'prediabetic state'. Prediabetic state form a part of syndrome X, other components being obesity, hypertension, dyslipidaemia, hyperinsulinaemia and insulin resistance. The pathophysiology of prediabetes is similar to type 2 diabetes mellitus, two basic defects are insulin resistance and early beta cell failure. In prediabetes, the rapid oscillations of insulin secretion are lost and amplitude of large pulses are decreased. When insulin is delivered in a pulsatile fashion that mimics the normal rapid oscillation, its hypoglycaemic effects are greater. In prediabetes, the glycaemic excursions after each meal are high and early insulin responses to meals tend to be lower than normal but the second phase of insulin secretion is delayed and prolonged.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 2/physiopathology , Disease Progression , Glucagon-Like Peptide 1 , Glucose Intolerance/physiopathology , Glucose Tolerance Test , Humans , Hyperglycemia/physiopathology , Insulin/physiology , Insulin Resistance/physiology , Metabolic Syndrome/physiopathology , Prediabetic State/physiopathology
17.
International Journal of Diabetes and Metabolism. 2005; 13 (2): 93-95
in English | IMEMR | ID: emr-70931

ABSTRACT

Plasma insulin levels among type 2 diabetic patients are modulated by racial and ethnic factors. In contrast to the plethora of reported studies on plasma insulin levels among type 2 diabetic patients in technically advanced regions of the world, there is paucity of such information in Africa in general. To study insulin output among type 2 diabetic Nigerians. Forty type-2 diabetic and 36 healthy subjects underwent a standard oral glucose tolerance test [OGTT]. Fasting and post OGTT plasma insulin levels were measured using an ELISA technique. Integrated insulin responses were calculated using trapezoidal estimation to compute total insulin output. Student's t test was used to compare means; the level of statistical significance in each case was taken as p < 0.05. The age and sex distribution of diabetic patients and control subjects were similar [p >0.5]. Average duration of diabetes was 5.6 +/- 4.3 years [range 1 -20 years] Total insulin output was significantly lower among type 2 diabetic patients than in control subjects [360 +/- 82.1 microunits per ml and 745.1 +/- 109.0 micro-units per ml respectively P<0.00 1]. Type-2 diabetic patients in this study exhibit hypoinsulinaemia; this could be the explanation for the pattern of diabetic complications among type 2 diabetic Nigerians observed in previous studies


Subject(s)
Humans , Male , Female , Insulin/physiology , Insulin/blood
18.
Arq. bras. endocrinol. metab ; 48(6): 803-811, dez. 2004.
Article in Portuguese | LILACS | ID: lil-393738

ABSTRACT

O tecido adiposo é um órgão dinâmico que secreta vários fatores, denominados adipocinas. Eles estão relacionados, direta ou indiretamente, em processos que contribuem na aterosclerose, hipertensão arterial, resistência insulínica e diabetes tipo 2, dislipidemias, ou seja, representam o elo entre adiposidade, síndrome metabólica e doenças cardiovasculares. Na obesidade, os depósitos de gordura corporal estão aumentados, apresentando conseqüente elevação na expressão e secreção das adipocinas, proporcionalmente ao maior volume das células adiposas. Os diferentes depósitos de gordura, a saber: tecidos adiposos visceral, subcutâneo abdominal, subcutâneo glúteo-femural e intramuscular, possuem grau metabólico e endócrino diferenciados, podendo estar, portanto, interferindo de forma específica nos processos inerentes à adiposidade corporal em obesos e diabéticos. O presente trabalho visa discutir sobre o papel endócrino e metabólico de cada compartimento de tecido adiposo, de modo a avaliar a contribuição dos mesmos nas complicações inerentes à obesidade.


Subject(s)
Humans , Adipose Tissue/metabolism , Metabolic Diseases/etiology , Muscle, Skeletal/metabolism , Subcutaneous Tissue/metabolism , Viscera/metabolism , Adipose Tissue/anatomy & histology , Catecholamines/physiology , Insulin Resistance , Insulin/physiology , Muscle, Skeletal/anatomy & histology , Risk Factors , Subcutaneous Tissue/anatomy & histology , Viscera/anatomy & histology
19.
Article in English | IMSEAR | ID: sea-93153

ABSTRACT

NF-kappaB activation, and elevated concentrations of macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1(IL-1), IL-6, free radicals, inducible nitric oxide (iNO), and stress hyperglycemia occurs in sepsis and this leads to systemic inflammatory response and myocardial depression seen in sepsis and septic shock. Conversely, insulin suppresses production of MIF, TNF-alpha, IL-1, IL-6, and free radicals, enhances endothelial NO generation, and enhances the production of anti-inflammatory cytokines IL-4, and IL-10, corrects stress hyperglycemia and improves myocardial function. This supports my earlier proposal that insulin (with or without glucose and potassium) therapy to maintain euglycemia suppresses the inflammatory response, improves myocardial function, and thus, is of benefit in acute myocardial infarction, sepsis andseptic shock.


Subject(s)
Animals , Cardiomyopathies/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Insulin/physiology , Insulin Resistance , Sepsis/blood , Shock, Septic/blood
20.
Indian J Exp Biol ; 2001 Oct; 39(10): 1009-16
Article in English | IMSEAR | ID: sea-59617

ABSTRACT

The present study investigated the cause effect relationship between glycemic and algesic states. The hypo- and hyperglycemic conditions were induced physiologically through exercise (3 min swim at room temperature 28 degrees - 30 degrees C) and external dextrose (2 g/kg, ip) administration respectively in mice. Besides, flavone (50 mg/kg, sc) a known antinociceptive drug was chosen to study such a cause effect relationship. The anti-nociception was assessed by acetic acid assay, blood glucose measured using glucometer (Ames) and serum insulin by radioimmunoassay. The findings revealed that irrespective of the glycemic state whether hypo-, hyper, or euglycemic induced by swim stress, dextrose or flavone per se respectively, significant antinociceptive response was recorded. Pretreatment with flavone (50 mg/kg, sc) always exhibited a tendency to reverse the hyperglycemia, if any, but enhanced the antinociceptive response either after swim stress or after dextrose. These data support the contention that changes in the glycemic state in acute condition is not responsible for antinociceptive response and thereby suggesting dissociation between these two parameters. Extended studies estimating serum insulin level after the above mentioned maneuvers showed a significant rise whenever antinociceptive response was recorded irrespective of the glycemic state. It is suggested that serum insulin level, a hormonal parameter rather than the blood glucose level, which is a metabolic parameter, appears more reliable. It appears that the changes in serum insulin level produced by various treatments may have a relationship with the antinociceptive response. However, this study has the limitation that the results can apply only for acute conditions and extrapolation to clinical conditions is debatable.


Subject(s)
Acetic Acid/toxicity , Analgesics/pharmacology , Animals , Blood Glucose/physiology , Flavonoids/pharmacology , Glucose/pharmacology , Hyperglycemia/physiopathology , Hypoglycemia/physiopathology , Insulin/physiology , Male , Mice , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Pain/chemically induced , Pain Threshold/physiology , Radioimmunoassay , Swimming
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