Ferulic acid enhances insulin secretion by potentiating L-type Ca2+ channel activation / 中西医结合学报

OBJECTIVE@#To investigate the effect of ferulic acid, a natural compound, on pancreatic beta cell viability, Ca2+ channels, and insulin secretion.@*METHODS@#We studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay. The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca2+ channels and insulin secretion, respectively.@*RESULTS@#Ferulic acid did not affect cell viability during exposures up to 72 h. The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca2+ channel current, shifting its activation curve in the hyperpolarizing direction with a decreased slope factor, while the voltage dependence of inactivation was not affected. On the other hand, ferulic acid have no effect on T-type Ca2+ channels. Furthermore, ferulic acid significantly increased insulin secretion, an effect inhibited by nifedipine and Ca2+-free extracellular fluid, confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca2+ influx through L-type Ca2+ channel. Our data also suggest that this may be a direct, nongenomic action.@*CONCLUSION@#This is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca2+ channel current in pancreatic β cells by enhancing its voltage dependence of activation, leading to insulin secretion.

Asiatic acid improves insulin secretion of β cells in type 2 diabetes through TNF- α/Mfn2 pathway / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM).@*METHODS@#The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α.@*RESULTS@#Asiatic acid with the dose of 25 mg·kg－1·d－1 had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α.@*CONCLUSIONS@#Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway.

Myricitrin and Its Solid Lipid Nanoparticle Increase Insulin Secretion and Content of Isolated Islets from the Pancreas of Male Mice

Abstract Glucose exposure induces toxic effects on the function of the pancreatic islets. Moreover, myricitrin as a flavonoid glycoside may have favorable effects on insulin secretion of Langerhans islets. The present study aimed to investigate the effect of Myricitrin and its solid lipid nanoparticles (SLN) on the insulin secretion as well as the content of isolated pancreatic islets from male mice. In this experimental study, Langerhans islets were separated from adult male NMRI mice using the collagenase method. The insulin secretion and content of islets were assessed in glucose-containing medium (2.8, 5.6, and 16.7mM). Further, islets treated were prepared by the administration of Myricitrin and its SLN (1, 3 and 10µM). Myricitrin 3µM, and SLN containing Myricitrin 3 and 10µM increased insulin secretion in medium containing glucose concentration 2.8mM. Accordingly, this variable increased in Myricitrin 3 and 10µM, SLN containing Myricitrin 1, 3, and 10µM utilization as well as glucose concentration 5.6mM. Afterward, the insulin secretion increased in medium containing 16.7mM glucose after the addition of Myricitrin and SLN containing Myricitrin 1, 3, and 10µM. Also, the insulin content increased in Myricitrin and SLN containing Myricitrin 1, 3, and 10µM administered groups in all medium containing glucose concentrations. Myricitrin and its SLN increased islets insulin secretion and content in low, moderate, and high glucose concentration mediums

Effect of free fatty acids on insulin secretion, insulin sensitivity and incretin effect - a narrative review

ABSTRACT Deleterious effects of free fatty acids, FFAs, on insulin sensitivity are observed in vivo studies in humans. Mechanisms include impaired insulin signaling, oxidative stress, inflammation, and mitochondrial dysfunction, but the effects on insulin secretion are less well known. Our aim was to review the relationship of increased FFAs with insulin resistance, secretion and mainly with the incretin effect in humans. Narrative review. Increased endogenous or administered FFAs induce insulin resistance. FFAs effects on insulin secretion are debatable; inhibition and stimulation have been reported, depending on the type and duration of lipids exposition and the study subjects. Chronically elevated FFAs seem to decrease insulin biosynthesis, glucose-stimulated insulin secretion and β-cell glucose sensitivity. Lipids infusion decreases the response to incretins with unchanged incretin levels in volunteers with normal glucose tolerance. In contrast, FFAs reduction by acipimox did not restore the incretin effect in type-2 diabetes, probably due to the dysfunctional β-cell. Possible mechanisms of FFAs excess on incretin effect include reduction of the expression and levels of GLP-1 (glucagon like peptide-1) receptor, reduction of connexin-36 expression thus the coordinated secretory activity in response to GLP-1, and GIP (glucose-dependent insulinotropic polypeptide) receptors downregulation in islets cells. Increased circulating FFAs impair insulin sensitivity. Effects on insulin secretion are complex and controversial. Deleterious effects on the incretin-induced potentiation of insulin secretion were reported. More investigation is needed to better understand the extent and mechanisms of β-cell impairment and insulin resistance induced by increased FFAs and how to prevent them.

Utilidad de la prueba de tolerancia de comida mixta con Nutrial I para la evaluación de la función de las células beta en diabetes tipo 1 / Usefulness of the tolerance test of mixed food with Nutrial I for the assessment of beta cells function in diabetes type 1

RESUMEN Introducción: La prueba de tolerancia de comida mixta es considerada la prueba de oro para la medición de la producción de insulina endógena en pacientes con diabetes tipo 1. Objetivo: Determinar la utilidad de la prueba de tolerancia de comida mixta con Nutrial I para evaluar la función de las células ß en diabéticos tipo 1 de diagnóstico reciente y la relación de esa función con algunas características clínicas y bioquímicas. Métodos: Se estudiaron variables bioquímicas como la glucemia, hemoglobina glucosilada (HbA1c), péptido C y fracciones lipídicas. La prueba de tolerancia de comida mixta con Nutrial I se aplicó a 18 sujetos con diabetes tipo 1 de diagnóstico reciente y a 8 voluntarios con edades comprendidas entre 19 y 35 años. El consumo del suplemento Nutrial I se calculó según el peso del paciente. Se obtuvieron muestras para glucemia y péptido C a los -10, 0, 30, 60, 90 y 120 minutos. Resultados: Se observaron concentraciones elevadas de glucemia y disminuidas de péptido C durante la prueba de tolerancia de comida mixta en los diabéticos tipo 1 de diagnóstico reciente, en comparación con los voluntarios, así como, diferencias en las áreas bajo la curva de péptido C (AUC-pc) (p= 0,001). En los diabéticos tipo 1 de diagnóstico reciente se evidenció una correlación negativa entre el AUC-pc con los niveles de glucemia en ayunas (r= -0,747; p ( 0,0001) y la HbA1c (r= -0,535; p= 0,022). Por el contrario, se encontró una correlación positiva entre el AUC-pc y el péptido C en ayunas (r= 0,722; p= 0,001). El AUC-pc después de la prueba de tolerancia de comida mixta es mayor en los sujetos con glucemia en ayunas si GA < 7 mmol/L con respecto a los sujetos con glucemia en ayunas ( 7 mmol/L (p= 0,012). Conclusiones: El empleo del Nutrial I en la prueba de tolerancia de comida mixta fue útil en la evaluación de la función de las células β en diabéticos tipo 1 de diagnóstico reciente. Los valores bajos de glucemia en ayunas durante esta prueba son marcadores indirectos de una función residual de células ( más conservada en los diabéticos tipo 1 de diagnóstico reciente(AU)

ABSTRACT Introduction: The tolerance test of mixed food is considered the gold standard for the measurement of endogenous insulin production in patients with diabetes type 1. Objective: To determine the usefulness of the tolerance test of mixed food with Nutrial I to assess the ß-cells function in patients with diabetes type 1 of recent diagnosis and the relation of this function with some clinical and biochemical characteristics. Methods: There were studied biochemical variables as the blood glucose, glycosylated haemoglobin (HbA1c), C-peptide and lipid fractions. The tolerance test of mixed food with Nutrial I was applied to 18 individuals with diabetes type 1 of recent diagnosis and in 8 volunteers aged between 19 and 35 years old. The consumption of Nutrial I supplement was calculated according to the weight of the patient. Samples were obtained for blood glucose and C-peptide at -10, 0, 30, 60, 90 and 120 minutes. Results: There were observed high concentrations of glycemia and decreased amounts of C-peptide during the tolerance test of mixed food in recently diagnosed type 1 diabetics in comparison with the volunteers, as well as differences in areas under the curve of C-peptide (AUC-pc) (p= 0.001). In the recently diagnosed type 1 diabetics was evident a negative correlation between the AUC-pc with fasting plasma glucose levels (r= -0,747; p(0.0001) and HbA1c (r= -0,535; p= 0.022). On the contrary, it was found a positive correlation between the AUC-pc and fasting C-peptide (r = 0.722; p = 0.001). The AUC-pc after the tolerance test of mixed food was greater in subjects with fasting blood glucose < 7 mmol/L with respect to the subjects with fasting blood glucose ( 7 mmol/L (p= 0.012). Conclusions: The use of Nutrial I in the tolerance test of mixed food was useful in the assessment of the role of the β-cells in patients with recently diagnosed diabetes type 1. Low values of fasting blood glucose during this test are indirect markers of a residual function of (cells more preserved in type 1 diabetics of recent diagnosis(AU)

Evaluating the effects of vanadyl sulfate on biomarkers of oxidative stress and inflammation in renal tissue of rats with diabetes type 2

Vanadyl sulfate (VS) is an ingredient in some food supplements and experimental drugs. This study was designed to assay the effects of VS on biomarkers of oxidative stress and inflammation in renal tissue of rats with diabetes type 2. 30 male Wistar rats were divided into three equal groups as follow: non-diabetics, non-treated diabetics and VS-treated diabetics. Diabetes type 2 has been induced through high fat diet and fructose in the animals. Diabetic rats were treated with 25 mg/kgBW of VS in water for 12 weeks. At the end of study, glucose and insulin were measured using commercially available kits in serum and biomarkers of oxidative stress and inflammation in renal homogenates of animals were measured by related methods. Compared to controls, glucose and insulin were increased significantly in non-treated diabetic rats (p-value <0.05) that showed the induction of diabetes type 2 in rats. The results showed that in VS-treated diabetic rats compared to the non-treated diabetic group, vanadyl sulfate significantly reduced the glucose and insulin secretion and changed renal inflammatory and oxidative markers, except protein carbonyl so that we couldn't find any significant changes. Our study showed that vanadyl supplementation had positive effects on oxidative stress and inflammation biomarkers in kidney of diabetic rats

The relationships between hemoglobin and insulin resistance, glucose effectiveness, and first- and second-phase insulin secretion in adult Chinese

ABSTRACT Objective We denote the four major factors related to the development of type 2 diabetes (T2D) as "diabetes factor" (DF); increased insulin resistance (IR); decreased glucose effectiveness (GE); and the first-and-second-phase of insulin secretion (FPIS, SPIS). The level of hemoglobin (Hb) was found to be related to IR and FPIS, but no-known studies focused on its role in relation to SPIS and GE. In this study, we aim to evaluate the relationships between Hb and all four DFs in the same individual. Subjects and methods We randomly enrolled 24,407 men and 24,889 women between 30 and 59 years old. IR, FPIS, SPIS and GE were measured according to equations published in our previous studies. To compare the slopes between Hb and the four DFs with different units, we converted their units to percent of change per unit of increased Hb. Results Age, HDL-cholesterol and GE were higher in women; BMI, blood pressure, LDL-cholesterol, TG, Hb, FPIS, SPIS and IR were higher in men. After they were converted into percentage, the closeness of their relationships to Hb, from the highest to the lowest, were GE, IR, FPIS and SPIS for women and IR, GE, FPIS and SPIS for men. GE was the only one negatively related to Hb. Conclusions Our data showed that IR, FPIS and SPIS were both positively and, GE negatively, related to the Hb in adult Chinese. For women, GE had the closest association with Hb; for men, it was IR. Both phases of insulin secretion had relatively weaker relationships than IR and GE.

Complicaciones musculoesqueléticas de la diabetes mellitus / Musculoskeletal complications of diabetes mellitus

Introducción: La diabetes se concibe como una enfermedad endocrina y metabólica determinada genéticamente y distinguida por un déficit parcial o total en la secreción de insulina, hormona segregada por las células beta del páncreas. Poco se ha escrito sobre las complicaciones musculoesqueléticas provocadas por esta enfermedad. Objetivo: reflexionar sobre las principales complicaciones musculoesqueléticas provocadas por la diabetes mellitus. Desarrollo: los síndromes periarticulares, los síndromes articulares y esqueléticos, los síndromes periarticulares y los síndromes musculares destacan entre las principales complicaciones musculoesqueléticas provocadas por la diabetes mellitus. Conclusiones: Resultan habituales los desórdenes reumáticos en la diabetes mellitus y sus tipologías se consideran amplias. Muchas de estas características están vinculadas con la duración de la enfermedad, al escaso control de la condición y a otras manifestaciones crónicas de la diabetes. Se establece como posible en la mayoría de casos que un control apropiado de la diabetes puede prevenir la mayoría de estas condiciones. Generalmente, el médico general se orienta a las complicaciones cardiovasculares, renales y oculares del paciente diabético por representar estas una gran afectación en la morbilidad y mortalidad. No obstante, las complicaciones reumáticas en los diabéticos pueden producir una discapacidad considerable. Por esta razón, se les debe incluir en el diseño de estrategias para perfeccionar el manejo clínico y la calidad de vida de los pacientes diabéticos(AU)

Introduction: Diabetes is conceived as a genetically determined endocrine and metabolic disease and distinguished by a partial or total deficit in the secretion of insulin, a hormone secreted by the beta cells of the pancreas. Little has been written about the musculoskeletal complications caused by this disease. Objective: to reflect on the main musculoskeletal complications caused by diabetes mellitus. Development: periarticular, joint and skeletal, periarticular and muscular syndromes stand out among the main musculoskeletal complications caused by diabetes mellitus. Conclusions: Rheumatic disorders are common in diabetes mellitus and their typologies are considered broad. Many of these characteristics are linked to the duration of the disease, the poor control of the condition and other chronic manifestations of diabetes. It is established as possible in most cases that an appropriate control of diabetes can prevent most of these conditions. Generally, the general practitioner is oriented to the cardiovascular, renal and ocular complications of the diabetic patient because they represent a great affectation in morbidity and mortality. However, rheumatic complications in diabetics can produce considerable disability. For this reason, they should be included in the design of strategies to improve the clinical management and quality of life of diabetic patients(AU)

El esqueleto como órgano endocrino: funciones metabólicas de la osteocalcina / The skeleton as an endocrine organ: metabolic functions of osteocalcin

El esqueleto es uno de los sistemas más grandes de un vertebrado y, como tal, es razonable especular que no puede funcionar aislado del resto del organismo. De hecho, sabemos que existen sistemas complejos de regulación cruzada entre el esqueleto y muchos otros órganos. Hoy poseemos herramientas que nos permiten realizar supresión genética en células o tejidos específicos. Esto nos ha permitido comprender cómo los órganos se comunican entre sí y ha revitalizado el concepto de fisiología del organismo como un todo. Efectivamente, los últimos años han sido testigos del descubrimiento de funciones inesperadas que ejerce el esqueleto y que afectan al organismo en su totalidad. Una de tales funciones reconocidas recientemente es el control del metabolismo energético, a través de la secreción de osteocalcina. La osteocalcina es una hormona producida por los osteoblastos que regula la secreción de insulina, la sensibilidad a esta hormona y el metabolismo energético. Los hallazgos iniciales suscitaron varias preguntas fundamentales sobre la naturaleza de la acción de la insulina sobre el hueso. Pero esto solo fue la punta del iceberg. Efectivamente, más adelante se descubrió, mediante el análisis de ratones que carecen del receptor de insulina (Ins R) solamente en osteoblastos, que la acción de la insulina sobre estas células favorecía la homeostasis de la glucosa en todo el cuerpo. Es importante destacar que esta función de la insulina en los osteoblastos opera mediante la regulación negativa de la carboxilación y la biodisponibilidad de la osteocalcina. Más aún, se observó que las vías de señalización de la insulina en los osteoblastos regulan positivamente no solo la formación sino también la resorción del hueso. Curiosamente, parece que las vías de señalización de la insulina en osteoblastos pueden inducir la activación de la osteocalcina mediante la estimulación de la actividad de los osteoclastos. De hecho, el bajo pH generado durante la resorción ósea es suficiente para desencadenar la descarboxilación (y subsiguiente activación) de la osteocalcina. En breve discutiremos dos nuevas proposiciones: 1) los osteoblastos son un blanco utilizado por la insulina para controlar la homeostasis de la glucosa en todo el organismo y 2) la resorción ósea desempeña un papel fundamental en la regulación de la activación de la osteocalcina. (AU)

The skeleton is one of the biggest systems in a vertebrate animal and, as such, it is reasonable to speculate that it cannot function isolated from the rest of the organism. In fact, we know that complex systems exist for the cross-regulation between the skeleton and several other organs. Today, we have the tools that allow us to perform genetic suppression in specific cells or tissues. This has allow us understand the mechanisms by which the organs communicate with each other and has revitalized the concept of organismal physiology as a whole. Studies conducted in recent years have uncovered unexpected functions performed by the skeleton. One of these is the control of global energy metabolism, through the secretion of osteocalcin, a protein produced by osteoblasts that acts as a hormone regulating insulin secretion, insulin sensitivity and energy expenditure. The evidence comes from the analysis of mice lacking insulin receptor (InsR) exclusively in osteoblasts. These mice have a global metabolic phenotype demonstrating that the action of insulin in osteoblasts promotes the homeostasis of glucose throughout the body. This action of insulin in osteoblasts is mediated by the negative regulation of the carboxylation (and bioavailability) of osteocalcin. The decarboxylation (and activation) of osteocalcin, in turn, occurs in the osteoclastic resorption pit. Briefly: the osteoblast is a target used by insulin to control the homeostasis of glucose throughout the body and bone resorption is the mechanism that regulates the activation of osteocalcin. (AU)

Prevalence of pancreatic autoantibodies in non-diabetic patients with autoimmune thyroid disease and its relation to insulin secretion and glucose tolerance

ABSTRACT Objective We evaluated the prevalence of glutamic acid decarboxylase (GADA) and tyrosine phosphatase-protein antibodies (IA2A), their titers and their relation to first phase insulin response (FPIR) and glucose tolerance in autoimmune thyroid diseases (ATDs) patients. Subjects and methods Graves' disease (GD; n = 181) and Hashimoto's thyroiditis (HT; n = 143) patients in addition to healthy controls (n = 93) were studied. Secondly, FPIR and oral glucose tolerance tests (OGTT) were performed in 11 anti-pancreatic islet-cell (+) and in 20 anti-pancreatic-cell (-) patients. Results There was a non significant trend for higher prevalence of GADA positivity in GD vs HT (7.2% vs 2% p = 0.06), but the GADA titers were higher in HT. We also did not find a significant difference in IA2 prevalence (0.7% vs 0.0%) between these two groups or compared to the control group. In the subsequent analysis, low FPIR was found in 10% of these patients but without statistical difference for OGTT between pancreatic antibody-positive and -negative patients. Conclusion A trend for greater prevalence of GADA was observed for GD patients than for HT or control. However, the titers of these autoantibodies were higher in HT patients, but there was no significant relation to insulin secretion and glucose tolerance at that moment and stage of autoimmune diseases.

Jiawei Erzhiwan improves menopausal metabolic syndrome by enhancing insulin secretion in pancreatic β cells / 中国天然药物

Menopausal metabolic syndrome (MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases (CVD) and type II diabetes mellitus (T2DM). Erzhiwan (EZW), composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan (JE). The present study was designed to determine the anti-MMS effects of JE using ovariectomized (OVX) adult female rats that were treated with JE for 4 weeks, and β-tc-6 cells and INS cells were used to detected the protect effectiveness of JE. Our results showed JE could increase insulin sensitivity and ameliorated hyperlipidemia. Metabolomics analysis showed that the serum levels of branched and aromatic amino acids were down-regulated in serum by JE administration. Moreover, JE enhanced the function of islet β cells INS-1 and β-tc-6, through increasing the glucose stimulated insulin secretion (GSIS), which was abolished by estrogen receptor (ER) antagonist, indicating that JE functions were mediated by ER signaling. Additionally, JE did not induce tumorigenesis in rat mammary tissue or promoted proliferation of MCF-7 and Hela cells. In conclusion, our work demonstrated that JE ameliorated OVX-induced glucose and lipid metabolism disorder through activating estrogen receptor pathway and promoting GSIS in islet β cells, thus indicating that JE could be a safe and effective medication for MMS therapy.

MicroRNA and metabolism regulation / 中南大学学报(医学版)

MicroRNAs have been identified as a new class of regulatory molecules that affect many biological functions by interferring the target gene expressions. Latest studies demonstrate that microRNAs can influence many pivotal bio-processes and deeply involve in the metabolism of glucose, lipid and amino acid and biological oxidation. For glucose metabolism, microRNAs are related to insulin secretion, insulin sensitivity, glucose uptake, glycolysis, oxidation and mitochondrial function. For lipid matebolism, microRNAs can regulate the target genes related to lipid biosynthesis, catabolism and transportation. MicroRNAs can influence glutamine catabolism.

Insulinotrophic and hypolipidemic effects of Ecklonia cava in streptozotocin-induced diabetic mice

OBJECTIVE@#To explore the anti-diabetic activity of Ecklonia cava (EC) in streptozotocin (STZ)-induced diabetic mice.@*METHODS@#Diabetes was induced by a single intraperitoneal injection of STZ (90 mg/kg). Normal and diabetic mice were treated with 0%, 3%, and 5% EC diet for 4 weeks. Serum glucose and insulin concentrations, serum lipid profile, oral glucose tolerance test, and liver and pancreatic β-cell histopathological observations were performed. In addition, in vitro glucose-induced insulin secretion was determined using pancreatic β-islet cells.@*RESULTS@#EC supplementation significantly and dose-dependently decreased serum glucose concentration, and improved glucose homeostasis in diabetic mice by preventing loss of β-cell mass resulting in increase of insulin secretion. The triglyceride and total cholesterol concentrations in the serum and liver were markedly reduced by EC treatment in STZ-diabetic mice. Moreover, LDL-, and HDL-cholesterol levels were ameliorated in EC supplemented diabetic mice. Liver steatosis induced by STZ was ameliorated by EC supplementation. Furthermore, in vitro insulinotrophic effect of EC extract was observed in pancreatic β-islets.@*CONCLUSIONS@#This study demonstrated that EC is a potent and efficacious hypoglycemic and hypolipidemic agent, and prevents the loss of β-cell mass resulting in increase of insulin secretary capacity.

Glucose-dependent insulinotropic peptide in Type 2 diabetes after gastric bypass surgery / 中南大学学报(医学版)

Glucose-dependent insulinotropic peptide (GIP), the incretins, is synthesized and released from the duodenum and proximal jejunum. Continual high-fat diet powerfully stimulated GIP secretion, leading to obesity and harmful lipid deposition in islet cells and peripheral tissues, and giving rise to insulin resistance and major disturbances in the secretion of insulin. We can improve Type 2 diabetes by compromising GIP action. The exclusion of proximal small intestine and reduction of GIP secretion may be the important reasons for Type 2 diabetes after gastric bypass surgery.

Variations of beta-cell early-phase insulin secretion in type 2 diabetic patients in different stages / 中南大学学报(医学版)

OBJECTIVE@#To explore the variations of early-phase insulin secretion in Type 2 diabetic patients in different stages.@*METHODS@#L-arginine stimulative test, fast blood glucose and body mass index (BMI) were evaluated in 40 nomal controls (NC) and 101 Type 2 diabetic patients. The diabetic patients were divided into three groups: newly diagnosed group (n = 35), effectively treated by sulfonylureas group (n = 32) , and secondary failure of sulfonylureas group (n = 34). The indexs of insulin resistance of homeostasis model assessment (HOMA-IR), beta-cell insulin secretion of homeostasis model assessment (HOMA-IS), and the acute insulin response (AIRARG) index were calculated. Some statistical comparisons were done among the 4 groups.@*RESULTS@#The indexs of HOMA-IR in each group of Type 2 diabetic patients were all higher than those in NC group (P < 0.01). The AIRARG indexs were obviously lower in Type 2 diabetic patients in different stages than those in NC group (P < 0.01), and the subsequence from the highest to the lowest among the groups of diabetic patients was: the newly diagnosed group, the effectively treated by sulfonylureas group, and the secondary failure of sulfonylureas group (P < 0.01). But there was no significant difference in indexs of HOMA-IS between the newly diagnosed group and the effectively treated by sulfonylureas group.@*CONCLUSION@#There is severe insulin resistance in Type 2 diabetic patients in each stage. The variations of early-phase insulin secretion manifest a vary procedure of obvious deterioration by degrees from the newly diagnosed group to the secondary failure of sulfonylureas group in Type 2 diabetic patients.

Angiotensin II receptor blocker valsartan enhances glucose induced insulin secretion

A number of antihypertensive drugs are known to be diabetogenic. This may contribute to less than expected decrease in the incidence of coronary heart disease with reduction in blood pressure with treatment in hypertensive patients. This study was aimed to determine the effects of a member, Valsartan, of a new class of drugs, angiotensin II receptor blocker, on glucose induced insulin secretion. Male albino rat pancreases were used. The isolated pancreases were perfused with Kreb's solution containing bovine albumin [200 mg/dl] with low glucose [60 mg/dl] followed by high glucose [300 mg/dl] at a rate of 4 ml/min. The dose of Valsartan used was based on the peak plasma level achieved in human at standard single oral dose of 80 mg daily, which was 1.64 mg/L. Five treatment groups were used: Control group, Valsartan at 10%, Valsartan at 100% and Valsartan at 10 times of the 1.64 mg/L, and Diazoxide 10 micro g/ml group. Insulin levels in the perfusate were measured by radioimmunoassay. Valsartan at all concentrations significantly increases glucose induced insulin secretion [p < 0.05]. Valsartan at 10%, Valsartan at 100% and Valsartan at 10 times of the 16.4 mg/L, increases glucose induced insulin secretion by 226.4%, 161.7% and 156.3%, respectively. Diazoxide, significantly inhibits glucose induced insulin secretion [p < 0.05]. Valsartan at all concentrations enhances glucose-induced insulin secretion in isolated rat pancreas technique

Potential relationship between peripheral blood mitochondrial DNA content and insulin resistance and secretion in offspring of type 2 diabetic patients

Both qualitative and quantitative changes in mitochondrial DNA [mtDNA] have been implicated in the pathogenesis of diabetes mellitus. In this study, we investigate whether peripheral blood mtDNA [pb-mtDNA] is decreased and if there is any relation between its content and the parameters of both insulin resistance and secretion in offspring of diabetic subjects. The pb-mtDNA content was measured by real time polymerase chain reaction with mitochondrial- specific fluorescent probe, normalized by a nuclear DNA, 28S rRNA gene, in 42 offspring of type 2 diabetic patients and 12 age-, sex- and body mass index [BMI]- matched normal subjects. The correlations between pb-mtDNA content and the parameters of insulin resistance and secretion were studied. Our results indicated that the level of pb-mtDNA was lower in offspring of diabetic subjects than in control subjects [1.230 +/- 0.05 vs. 1.513 +/- 0.02 in the offspring and control subjects, respectively, P <0.05]. Also, pb-mtDNA content was significantly correlated with logarithmically transformed insulin sensitivity index [r = 0.5, P<0.05], fasting C-peptide [r = -0.8, P<0.05], acute insulin response [r = -0.8, P<0.05] and late insulin response [r = -0.7, P <0.05] in offspring of diabetic subjects. In conclusion, quantitative mtDNA status might be a hereditary factor associated with type 2 diabetes and is correlated negatively with indexes of insulin resistance and insulin secretion in offspring of diabetic patients. So, pb-mtDNA content could serve as an indicator of insulin sensitivity and insulin secretion in those subjects