A cross-sectional study to assess beta-cell function in individuals with recently diagnosed young-onset type 2 diabetes mellitus and its’ complications / Journal of the ASEAN Federation of Endocrine Societies

Objective@#The primary objective was to assess beta-cell function of recently-diagnosed young-onset type 2 diabetes mellitus (T2DM) individuals using basal and stimulated C-peptide levels. The secondary objective was to examine the association between C-peptide with metabolic factors and diabetes complications.@*Methodology@#A cross-sectional study was conducted for young-onset T2DM individuals aged 18-35 years with a disease duration of not more than 5 years. Plasma C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. Continuous data were expressed as median and interquartile range (IQR). Categorical variables were described as frequency or percentage. Multivariable linear regression analysis was used to determine factors associated with C-peptide levels.@*Results@#113 participants with young-onset T2DM with a median (IQR) age of 29.0 (9.5) years and 24 (36) months were included in this study. The median (IQR) basal and stimulated C-peptide was 619 (655) pmol/L and 1231 (1024) pmol/L. Adequate beta-cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. We found hypertension, obesity and diabetic kidney disease (DKD) to be independently associated with higher C–peptide levels. In contrast, females, smokers, those on insulin therapy and with longer duration of disease had lower C–peptide levels.@*Conclusion@#Most recently diagnosed young-onset T2DM have adequate beta-cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggest insulin resistance as the key driving factor for complications.

Tres versiones del "Ogtt Squeezer", un programa para evaluar de un vistazo la información metabólica de la curva de tolerancia a la glucosa / Three versions of the "Ogtt Squeezer", a program to evaluate ataglance the metabolic information of the oral glucose tolerance test

El diagnóstico clínico de resistencia insulínica (RI) es difícil, ya que el Clamp no es aplicable a la clínica. El así llamado "síndrome metabólico", un predictor clínico de la RI, no identifica alrededor de la mitad de los sujetos afectados. Previamente, definimos adecuadamente (Análisis ROC) los niveles de corte diagnóstico de los siguientes predictores bioquímicos: HOMA1, HOMA2, QUICKI e ISI-Composite, a través de analizar datos de 90 sujetos (53 no resistentes y 37 resistentes) que tenían una medición directa de su resistencia insulínica (Test de supresión pancreática, TSP, Test de Reaven) y también, una curva de tolerancia a la glucosa oral (CTG). Los puntos de corte obtenidos exhibieron un mucho mejor desempeño diagnóstico comparados con los puntos de corte convencionales. También encontramos un predictor nuevo, simple, económico y eficiente, el I0*G60. Definimos la "normalidad metabólica" de la CTG usando las medianas de los valores de varios parámetros en 312 sujetos con un G120 dentro de los 2 primeros terciles del grupo de normo-tolerantes a la glucosa (NGT, n=468; G120: 51-110 mg/dL, los con mejor función beta insular). A las medianas de la función beta insular y de la sensibilidad insulínica se les asignó un valor de un 100%. Se calculó el % relativo de función beta insular (%RFBI) y el % relativo de sensibilidad insulínica (%RSI) del resto de la cohorte (n=573) contra estos valores de referencia. El "OGTT Squeezer" se escribió en Excel. Las glicemias y las insulinemias de la CTG fueron las entradas del programa. Las salidas fueron: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictores) y el índice insulinogénico, el índice de disposición, %RFBI y %RSI (parámetros). El programa también caracterizó la tolerancia glucídica de acuerdo a los criterios de la ADA 2003. El formato final del programa, HTML 5, facilita su uso. Desarrollamos tres versiones del programa: completa, abreviada y mínima.

Clinically, diagnosing insulin resistance (IR) is difficult since the Clamp is not applicable to clinical work. The so-called "Metabolic Syndrome", a clinical surrogate of IR, fails to identify around 50% of affected subjects. Previously, we properly defined (ROC Analysis) the diagnostic cut-offs of the following biochemical predictors: HOMA1, HOMA2, QUICKI, and ISI-Composite by analyzing data from 90 subjects (53 non-insulin-resistant and 37 insulin-resistant subjects) who had a direct measurement of insulin resistance (Pancreatic Suppression Test, PST, Reaven's Test), and also, an Oral Glucose Tolerance Test (OGTT). The resulting cut-offs exhibited much better performances compared with the conventional cut-offs. We also found a new, simple, inexpensive and efficient predictor, the I0*G60. We chose to define the "metabolic normalcy" of the OGTT by using the median values of several parameters in 312 NGT subjects with a G120 in the first 2 tertiles of the NGT group (n=468; G120: 51-110 mg/dL, those with the best beta-cell function). The median values of both Beta-Cell Function and Insulin Sensitivity of these subjects were assigned a 100% value. Both % Relative Beta-Cell Function (%RBCF) and % Relative Insulin Sensitivity (%RIS) of everyone else in the cohort (n=573) was calculated against these reference values. The "OGTT Squeezer" was written in Excel. The OGTT's glucose and insulin values served as the inputs of the program. The outputs were: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictors), and Insulinogenic Index, Disposition Index, %RBCF, and %RIS (parameters). Moreover, the program characterized the OGTT according to the ADA 2003 criteria. The HTML 5 format of the program facilitates its use. We developed 3 versions of the program: complete, abbreviated, and minimal versions.

Clinical characteristics, residual beta-cell function and pancreatic auto-antibodies in Thai people with long-standing type 1 diabetes mellitus / Journal of the ASEAN Federation of Endocrine Societies

@#Objectives. To describe the characteristics of long-standing T1DM in Thai patients and assess residual beta-cell function with status of pancreatic autoantibodies. Methodology. This is a cross-sectional study of Thai subjects with T1DM and disease duration ≥ 25 years seen at the Theptarin Hospital. Random plasma C-peptide and pancreatic auto-antibodies (Anti-GAD, Anti-IA2, and Anti-ZnT8) were measured. Patients who developed complications were compared with those who remained free of complications. Results. A total of 20 patients (males 65%, mean age 49.4±12.0 years, BMI 22.5±3.1 kg/m2, A1C 7.9±1.6%) with diabetes duration of 31.9±5.1 years were studied. Half of the participants remained free from any diabetic complications while the proportions reporting retinopathy, nephropathy, and neuropathy were 40%, 30%, and 15%, respectively. HDL cholesterol was significantly higher and triglyceride concentration significantly lower in patients who were free from diabetic nephropathy but not in those who were free from other complications. The prevalence rates of anti-GAD, anti- IA2, and anti-ZnT8 were 65%, 20%, and 10%, respectively. None of the patients who tested negative for both anti-GAD and anti-IA2 was positive for anti-ZnT8. Residual beta-cell function based on detectable random plasma C-peptide (≥ 0.1 ng/mL) and MMTT was found in only 3 patients (15%). There was no relationship between residual beta-cell function and protective effects of diabetic complications. Conclusion. Endogenous insulin secretion persists in some patients with long-standing T1DM and half of longstanding T1DM in Thai patients showed no diabetic complications. HDL cholesterol was significantly higher and triglyceride concentration significantly lower in patients who were free from diabetic nephropathy

Effect of Shenqi Compound on Islet β-cell Function in Type 2 Diabetic GK Rats / 中国实验方剂学杂志

Objective:To explore the effect of Shenqi compound on islet β-cell function in type 2 diabetic GK rats. The whole genome expression profile chip technology is used to explore the molecular mechanism of Shenqi compound regulating pancreatic islet cell function and provide theoretical basis for the prevention and treatment of type 2 diabetes with traditional Chinese medicine. Method:GK rats were fed with high-fat diet daily for 4 weeks. Rats were randomly selected from GK rats to detect random blood glucose and verified the success of type 2 diabetes model. Rats were divided into 4 groups， Wistar group， model group， Shenqi compound（1.44 g∙kg-1） group and west glenn（16 mg∙kg-1） group. After 8 weeks of gavage， the serum insulin（INS） levels were detected by enzyme-linked immunosorbent assay（ELISA）. The apoptosis of islet β cells was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling（TUNEL）fluorescence method. Differential gene detection uses whole-genome expression profiling chip technology in each group of rat pancreatic tissues， the mRNA transcription level of key differential genes is detected by Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with blank group， before gavage， 4 weeks， 8 weeks， GK rats have higher blood sugar in each group （P<0.01）.Gavage for 4 weeks and gavage for 8 weeks， compared with model group， the blood sugar of rats in each drug intervention group was lower （P<0.01）. Gavage for 8 weeks， compared with blank group， the INS level of model group was lower （P<0.01）. Compared with model group， the Shenqi compound group had a higher INS level， and the sitagliptin group had a higher INS level （P<0.01）. After gavage for 8 weeks， compared with the blank group， the number of pancreatic islet β-cell apoptosis in the model group was higher （P<0.05）. Compared with model group， the number of pancreatic islet β cell apoptosis in the Shenqi compound group and sitagliptin group was lower （P<0.05，P<0.01）. Gene chip and Real-time PCR tests both showed that phosphatidylinositol 3-kinase receptor 1（PIK3R1） was up-regulated in the Shenqi compound group/model group， and down-regulated in the sitagliptin group/model group， model group/blank group. Protein kinase B1（Akt1） was expressed in the Shenqi compound group/model The expression was up-regulated in the group， sitagliptin group/model group， and down-regulated in the model group/blank group. Conclusion:Shenqi compound which has the function of supplenmenting Qi and Yin and promoting the blood circulation， can inhibit the islet β cell apoptosis， improve islet β cell function， regulate insulin secretion， and prevent T2DM by up-regulating the expression of genes PIK3R1 and Akt1.

Pancreatic islet stereology: estimation of beta cells mass / Estereología de los islotes pancreáticos: estimación de la masa de células beta

Obesity and its comorbidities are becoming epidemic in the Western world. Beta cell mass estimation is an important indicator to track the progression of insulin resistance/type 2 diabetes, particularly in experimental studies, where it can be performed with stereological tools in an unbiased way. In this work, we present a simple protocol that can contribute to doing the practice of estimating the mass of beta cells more frequent and reproducible. As with any quantitative study, the necessary precautions regarding sampling and randomness must be respected.

La obesidad y sus comorbilidades se están convirtiendo en una epidemia en el mundo occidental. La estimación de la masa de células beta es un indicador importante para rastrear la progresión de la resistencia a la insulina/diabetes tipo 2, particularmente en estudios experimentales, donde se puede realizar con herramientas estereológicas de manera imparcial. En este trabajo presentamos un protocolo simple que puede contribuir a que la práctica de estimar la masa de células beta sea más frecuente y reproducible. Como en cualquier estudio cuantitativo, deben respetarse las precauciones necesarias con respecto al muestreo y la aleatoriedad.

Insulin resistance and β-Cell function of lean versus overweight or obese Filipino patients with newly diagnosed Type 2 Diabetes Mellitus / Journal of the ASEAN Federation of Endocrine Societies

Objectives@#To compare the level of insulin resistance and β-cell function between lean and overweight/obese Filipino patients with newly diagnosed type 2 diabetes mellitus (T2DM).@*Methodology@#This was a cross-sectional analytical study including newly diagnosed T2DM Filipino patients from St. Luke’s Medical Center - Quezon City. The patients were classified as either lean or overweight/obese. Age, sex, smoking history, anthropometric measures and blood pressure were obtained. Insulin resistance and β-cell function were determined using the homeostasis model assessment (HOMA). The original model (HOMA1) and the updated model (HOMA2) were used. @*Results@#A total of 80 subjects were included. There were 40 subjects in each group. The overweight/obese subjects had significantly higher mean insulin resistance (HOMA1-IR 9.8±11.7, HOMA2-IR 3.0±2.0) compared to the lean group (HOMA1-IR 2.9±1.5, HOMA2-IR 1.3±0.5). This was consistent in both HOMA1 and HOMA2 (p-values=0.001 and <0.001, respectively). The mean β-cell function of the overweight/obese patients was significantly higher than the lean subjects when using HOMA1 (lean=57.8±35.5, overweight/obese=93.6±66.4, p-value=0.003), but not in HOMA2 (lean=57.6±30.5, overweight/obese=74.8±45.7, p-value=0.051). Overweight/obesity increased HOMA1-IR by 4.0 and HOMA1-B by 46.1 (p-values= 0.002 and <0.001, respectively). Through the use of HOMA2, overweight/obesity increased HOMA2-IR by 1.4 and HOMA2-B by 29.1 (p-values<0.001). Being overweight/obese was also associated with significantly higher odds for developing greater insulin resistance (HOMA1-IR adjOR = 5.6, 95%CI= 1.7-19.2, p-value=0.005; HOMA2-IR adjOR=10.9, 95%CI=3.4-34.9, p-value<0.001) and lower odds for a decreased β-cell function (HOMA1-B adjOR = 0.2, 95%CI = 0.05-0.9, p-value=0.033; HOMA2-B adjOR=0.2, 95%CI=0.04-0.9, p-value=0.043) compared to being lean. @*Conclusion@#Newly diagnosed overweight/obese T2DM had higher mean insulin resistance and β-cell function compared to lean T2DM. Overweight/obesity was also associated with higher odds of developing insulin resistance and lower odds for a decreased β-cell function compared to being lean. The overweight/obese T2DM group also had worse metabolic profile manifested by higher FPG, HbA1c, SGPT and blood pressures compared to the lean T2DM group.

Effect of wheatgrass on DNA damage, oxidative stress index and histological findings in diabetic rats / Efecto del pasto de trigo sobre el daño del ADN, el índice de estrés oxidativo y los hallazgos histológicos en ratas diabéticas

This study was aimed to search the effect of wheatgrass on the Total Antioxidan (TAS)-Oxidan Status (TOS) and DNA damage in rat with diabetes. The rats used in the study were randomly divided into 4 groups that each of has 10 rats: Control group; 1 ml single dose phosphate-citrate buffer injected i.p (pH: 4.5), Diabetes group; 45 mg/kg single dose streptozotocin injected i.p., Wheatgrass group; was given oral wheatgrass (10 ml/kg/day) for 6 weeks, Diabetes +Wheatgrass group; 45 mg/kg single dose streptozotocin injected i.p. and wheatgrass (10 ml/kg/day) was given by oral during 6 weeks. After the process of experiment during 6 weeks, blood sample and pancreas tissue were taken. The analysis were done of blood glucose levels, TAS, TOS levels by colorimetric kits; DNA damage by ELISA kits in serum. The pancreas tissues were examined histopathologically. In the group of Diabetes+Wheatgrass was determined that the levels of glucose levels (p<0.001), TOS (p<0.05) and OSI (p<0.01) statistically decreased and heal histopatolojical compared to diabetes group. In the group of Wheatgrass was determined that the levels of TAS p<0.05 statistically increased from other groups. The statistical significance were not found in the level of serum 8OHdG differences between the groups. The beta cells were seen to increase in the group receiving wheatgrass for therapeutic purposes.As a conclusion, it was determined that wheatgrass strengthened the anti-oxidant defense system and reduced the glucose level in diabetic rats.

El objetivo de este estudio fue buscar el efecto del pasto de trigo sobre el estado total de antioxidantes (TAS) -Oxidan Status (TOS) y el daño del ADN en ratas con diabetes. Las ratas analizadas en el estudio se dividieron aleatoriamente en 4 grupos de 10 ejemplares cada uno: grupo control; 1 ml de tampón fosfato-citrato de dosis única inyectado i.p. (pH: 4,5)., Grupo diabetes; 45 mg / kg de estreptozotocina en dosis única inyectada i.p., grupo pasto de trigo; se administró pasto de trigo oral (10 ml / kg / día) durante 6 semanas, grupo diabetes + pasto de trigo; 45 mg / kg de estreptozotocina en dosis única inyectada i.p. y pasto de trigo (10 ml / kg / día) por vía oral durante 6 semanas. Después del proceso experimental durante 6 semanas, se tomaron muestras de sangre y tejido de páncreas. Se midieron los niveles de glucosa en sangre, TAS, y TOS mediante kits colorimétricos; El daño al ADN fue realizado por kits de ELISA en suero. Los tejidos del páncreas se examinaron histopatológicamente. En el grupo de diabetes + pasto de trigo se determinó que los niveles de glucosa (p <0,001), TOS (p <0,05) y OSI (p <0,01) disminuyeron estadísticamente y curaron histopatológicamente en comparación con el grupo de diabetes. En el grupo de pasto de trigo se determinó que los niveles de TAS p <0,05 se incrementaron estadísticamente con respecto a otros grupos. No fue estadísticamente significativo el nivel de las diferencias séricas de 8OHdG entre los grupos. Se observó que las células beta aumentaron en el grupo que recibió pasto de trigo con fines terapéuticos. Como conclusión, se determinó que el pasto de trigo fortaleció el sistema de defensa antioxidante y redujo el nivel de glucosa en las ratas diabéticas.

A comparative study of antihyperglycemic effect of Gymnema sylvestre and metformin in streptozotocin induced diabetic rats

Background: Diabetes mellitus (DM) is a metabolic disorder that has the phenotype of hyperglycemia. According to World Health Organization (WHO) there were 65.1 million diabetics in India in 2013, International Diabetes Federation estimates this to increase to 190 million by 2035. Although a number of drugs are available for treatment of DM, their cost and safety profile are major concern. Medicinal plants are used by clinicians for treatment of diabetes. Gymnema sylvestre (GS) extract has been reported to increase insulin levels in diabetic rats. This study was designed to compare the antihyperglycemic effect of Gymnema sylvestre with metformin.Methods: Diabetes was induced in Sprague-Dawley rats using streptozotocin 45mg/kg. Methanolic extract of Gymnema sylvestre 120mg/kg p.o. prepared using Soxhlet apparatus.Results: GS extract reduced blood glucose levels but not statistically significant. GS extract increased HDL and triglycerides, reduced both serum ALT and AST but no statistical significance seen. Metformin significantly increased serum urea, which was not seen in GS extract group. GS extract showed regenerative changes in pancreas, liver and kidney.Conclusions: The study investigation demonstrates that methanolic extract of GS possesses antihyperglycemic and hypolipidaemic activity and so it can be considered as a promising natural remedy in a prediabetic state and in mild hyperlipidaemia to prevent its progression. Increase in ? cell regeneration activity could be a probable mechanism of action. However, further long term clinical studies are recommended to define its possible role in diabetes mellitus and hyperlipidaemia. Role of GS as a potential hepatoprotective agent also needs further evaluation.

Molecular Basis of Pathogenesis of Diabetes Mellitus Type 2- a New Perspective

Decreased insulin secretion due to beta cell dysfunction of the pancreas and defective utilization of insulin due to insulin resistance / Hyperinsulinemia are two important issues in the pathogenesis of DM2. There are many explanations in the literature to account for these two observed phenomena and their interrelationship. DM2 is believed to occur due to a complex interplay of environmental andBehavioural factors in genetically predisposed persons. Among the prominent theories explaining the pathogenesis of DM2, the viscera- Portal hypothesis, the Ectopic fat hypothesis and the adipose tissue as an endocrinal gland are prominent. Besides, the role played by oxidative stress, metabolic stress, mitochondrial dysfunction, endoplasmic reticulum stress, etc. are also advanced. It is felt that basic to and at the core of all the observed facts, is the shift of energy metabolism from normal glycolysis to B- oxidation of fats. Hence, how B - oxidation prevails over glycolysis is the fundamental issue to be addressed together with its interrelationships with insulin resistance, as to which is the cause and which is the effect. At the molecular level, an attempt to find answers to the above questions is made in this paper.To this extent, the Randle fatty acid cycle (Substrate competition theory of Randle) is suitably modified and applied to explain the switch of Energy metabolisms in DM2 .Defective disulfide bond formation of the insulin receptor which makes it physiologically ineffective, is suggested as the cause of the insulin resistance where as the prevailing molecular mechanisms stress on post-receptor signaling defect. The cause and effect of both are discussed. This line is considered to be a departure from traditional approaches broached above and briefly outlined in this article.

Effects of metformin on insulin sensitivity and islet beta cell secretion in obesity patients / 基础医学与临床

Objective To investigate the effects of metformin on insulin sensitivity and secretion in patients with obesity and insulin resistance. Methods This study enrolled 42 obesity patients with insulin resistance who were regularly followed-up in Peking Union Medical College Hospital from September 2012 to May 2016. They were divided into two groups according to their different status of glucose metabolism: normal glucose tolerance( NGT) and impaired glucose regulation( IGR) . Life style intervention and metformin were given to all these patients. The antropometric and metabolic data were collected before treatment, 3 and 6 months after treatment respectively. Results 42 patients, aged (23.6±6.5) years, including 11 males and 31 females were enrolled. 19 of them were NGT and 23 were IGR (8 of IGT and 15 of IFG) . Among all these patients, fasting insulin was significantly higher at 3 months after treatment(P＜0.05).The same results were shown in group-NGT(P＜0.05). Fasting insulin was significantly lower at 6 months after treatment than at baseline among all patients( P＜0.05) . HOMA-IR showed no significant difference between the baseline and 3 months after treatment, but significantly higher at baseline and 3 months after treatment than 6 months after therapy( P＜0.001) . HOMA-beta was significantly( P＜0.001) lower be-fore treatment and 6 months treatment the effect was more significant than 3 months after treatment among all pa-tients. HOMA-beta was significantly lower at baseline in group-IGR than at baseline in group-NGT ( P＜0.05) . Conclusions The effect of metformin on insulin secretion is earlier than that of improving the insulin sensitivity in patients with obesity and insulin resistance. Metformin is more likely to promote insulin secretion in patients with normal glucose tolerance than those with IGR within 3 months of intervention.

Association of Serum Vitamin D with Insulin Resistance and Beta Cell Function in Korean Health Checkup Examinees / 農村醫學 地域保健

OBJECTIVES: This study was conducted to examine the association of serum Vitamin D with insulin resistance and β-cell function in Korean health checkup examinees. METHODS: This study subjects were 374 healthy adults (199 males, 175 females) over the age of 20, who visited a general hospital medical center located in Haenam-gun, Jeollanam-do. To find the association of Vitamin D with HOMA-IR and HOMA-β, the used statistical analysis were ANOVA and ANCOVA. RESULTS: Of the study subjects, the level of serum Vitamin D defined by deficient group, insufficient group and sufficient group was 38.5%, 48.1% and 13.4%, respectively. According to the level of serum Vitamin D, the mean values of HOMA-IR were 1.92±1.08 in sufficient group, 1.99±1.04 in the insufficient group and 2.91±1.05 in deficient group and there were statistically significant different(p<0.001). The mean values of HOMA-β were 84.69±1.07 in sufficient group, 78.41±1.04 in the insufficient group and 80.48±1.04 in deficient group, and there were not significant. As a result of ANCOVA, adjusted mean of HOMA-IR were statistically significant different (p<0.001), but those of HOMA-β were not statistically significant according to the level of serum Vitamin D. CONCLUSIONS: The insufficient level of serum Vitamin D was relatively high in healthy adults who live in rural area, and it was found that HOMA-IR significantly increased when Vitamin D was deficient. To prevent insulin resistance or diabetes, it is necessary to provide sufficient information related to sufficient production of Vitamin D such as Vitamin D supplement, sun exposure, food intake and etc.

Oral insulin improves metabolic parameters in high fat diet fed rats

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.

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.

Antioxidant, anti-alpha-glucosidase and pancreatic beta-cell protective effects of methanolic extract of Ensete superbum Cheesm seeds

Objective To investigate the antioxidant, anti-α-glucosidase and pancreatic β-cell protective potential of Ensete superbum (E. superbum) seeds. Methods A variety of in vitro assays including radical scavenging, reducing power potential, phenolic content determination, α-glucosidase assay and pancreatic β-cell (1.4E7 cells) viability were employed for assessing the effect of methanolic extract of E. superbum seeds. Results The radical scavenging and reducing power effects comparable with the standard rutin were obtained while the enzyme inhibitory activity of the extract was 68-fold better than the standard antidiabetic drug, acarbose. The seed extract of E. superbum was packed-full of polyphenols with mean percentage gallic acid equivalent value of (38.2 ± 1.8) (n = 3). The protection of pancreatic cells from massive onslaught of hydrogen peroxide was far superior to that obtained for rutin. Conclusions The reputed antidiabetic therapeutic uses of the seeds extract of E. superbum may be justified on the basis of inhibition of carbohydrate enzymes, antioxidant effects and pancreatic β-cell protection.

Dynamic associations of mitochondria-endoplasmic reticulum in maintenance of pancreatic beta cell homeostasis / 药学学报

The appropriate regulation of intracellular bioenergy and nutrient metabolism is a basic requirement for proper function and survival of pancreatic beta cells, where mitochondria-endoplasmic reticulum (ER)-associations play crucial roles. Mitochondria are changed dynamically according to intracellular energy and nutrients, which provides material foundation for energy homeostasis; while ER regulates metabolic enzymes and protein synthesis in different pathways. This review sheds light upon the development of mitochondria-ER associations and its role in the regulation of insulin secretion in pancreatic beta cell. The impact on beta cell viability is discussed. Interruption of calcium and redox oxidative species results in reduction of glucose-stimulated insulin secretion, while intracellular calcium levels could be partial altered by depleting calcium from the ER. Given the tight link between ER and mitochondria, the association are crucial to the homeostasis and are an indicator of overall beta cell status, with a potential as a novel drug target for treatment of type 2 diabetes mellitus.

Beneficial Effects of Aerobic Exercise Training Combined with Rosiglitazone on Glucose Metabolism in Otsuka Long Evans Tokushima Fatty Rats

BACKGROUND: Regular aerobic exercise is essential for the prevention and management of type 2 diabetes mellitus and may be particularly beneficial for those treated with thiazolidinediones, since it may prevent associated weight gain. This study aimed to evaluate the effect of combined exercise and rosiglitazone treatment on body composition and glucose metabolism in obese diabetes-prone animals. METHODS: We analyzed metabolic parameters, body composition, and islet profiles in Otsuka Long Evans Tokushima Fatty rats after 28 weeks of aerobic exercise, rosiglitazone treatment, and combined exercise and rosiglitazone treatment. RESULTS: Combined exercise with rosiglitazone showed significantly less increase in weight and epididymal fat compared to rosiglitazone treatment. Aerobic exercise alone and combined rosiglitazone and exercise treatment led to similar retention of lean body mass. All experimental groups showed a decrease in fasting glucose. However, the combined exercise and rosiglitazone therapy group showed prominent improvement in glucose tolerance compared to the other groups. Rescue of islet destruction was observed in all experimental groups, but was most prominent in the combined therapy group. CONCLUSION: Regular aerobic exercise combined with rosiglitazone treatment can compensate for the adverse effect of rosiglitazone treatment and has benefit for islet preservation.

Antioxidant, anti-alpha-glucosidase and pancreatic beta-cell protective effects of methanolic extract of Ensete superbum Cheesm seeds

Objective: To investigate the antioxidant, anti-a-glucosidase and pancreatic b-cell protective potential of Ensete superbum (E. superbum) seeds. Methods: A variety of in vitro assays including radical scavenging, reducing power potential, phenolic content determination, a-glucosidase assay and pancreatic b-cell (1.4E7 cells) viability were employed for assessing the effect of methanolic extract of E. superbum seeds. Results: The radical scavenging and reducing power effects comparable with the stan-dard rutin were obtained while the enzyme inhibitory activity of the extract was 68-fold better than the standard antidiabetic drug, acarbose. The seed extract of E. superbum was packed-full of polyphenols with mean percentage gallic acid equivalent value of (38.2 ± 1.8) (n = 3). The protection of pancreatic cells from massive onslaught of hydrogen peroxide was far superior to that obtained for rutin. Conclusions: The reputed antidiabetic therapeutic uses of the seeds extract of E. superbum may be justified on the basis of inhibition of carbohydrate enzymes, anti-oxidant effects and pancreatic b-cell protection.

Gestational diabetes reduces pancreatic beta cells in rat offspring / La diabetes gestacional reduce las células beta pancreáticas en crías de ratas

Previous study has shown the adverse effects of gestational diabetes on hippocampal and spinal cord neuronal density in animal model. This study was conducted to determine the effect of gestational diabetes on beta cells in rat pancreas in early postnatal life. In this experimental study, 10 dams randomly allocated into control and diabetic groups on day 1 of gestation. Five dams in diabetic group received 40 mg/kg/BW of streptozotocin (intraperitoneally) and control animals received normal saline. Six of 28 and 56-day-old offspring of each gestational diabetes mellitus and controls were randomly scarified and sections were taken from the pancreas and stained using Gomorra's method. The density of beta cells and number and area of pancreatic islets were evaluated by quantitative computer-assisted morphometric method. The density of beta cells of 28-day-old offspring pancreas significantly reduced from 96.23±5.0 in control group to 71.5±5.3 cells in 10000 mm2 area of islet in diabetic group (P <0.01). The number of the pancreatic islets of in gestational diabetes (15.25±3.7) significantly reduced in comparison with the controls (8.61±0.7). The density of beta cells of 56-day-old offspring pancreas significantly reduced from 105.33±8.6 in control group to 62.12±5.9 in diabetic group (P <0.01). The number of the pancreatic islets of in gestational diabetes (13.5±0.5) significantly reduced compared to controls (6.75±1.7) (P <0.01). This study revealed that gestational diabetes loss the number of the beta cells in 28 and 56-day-old rat offspring.

Estudios previos han mostrado los efectos adversos de la diabetes gestacional en la densidad neuronal del hipocampo y de la médula espinal en modelos animales. Este estudio se llevó a cabo para determinar el efecto de la diabetes gestacional en las células beta del páncreas de rata en vida postnatal temprana. En este estudio experimental, 10 ratas fueron asignadas al azar a los grupos control y diabético en el día 1 de gestación. Cinco ratas del grupo diabético recibieron 40 mg/kg/BW de estreptozotocina (intraperitonealmente), mientras que los animales del grupo control recibieron solución salina normal. Seis de los descendientes, de 28 y 56 días de edad, de cada grupo, diabetes mellitus gestacional y control, se escarificaron al azar y se tomaron secciones del páncreas, que se tiñeron usando el método de Gomorra. La densidad de las células beta y el número y área de islotes pancreáticos fueron evaluados a través de método cuantitativo asistido por computadora morfométrica. La densidad de células beta del páncreas en las crías de 28 días disminuyó significativamente de 96,23 ± 5,0 en el grupo de control a 71,5 ± 5,3 células en el grupo diabético, en 10000 mm2 de área de islote (P <0,01). El número de islotes pancreáticos de la diabetes gestacional (15,25 ± 3,7) se redujo significativamente en comparación con los controles (8,61 ± 0,7). La densidad de células beta del páncreas en las crías de 56 días de edad se redujo de 105,33 ± 8,6 en el grupo de control a 62,12 ± 5,9 en el grupo diabético (P <0,01). El número de islotes pancreáticos en el grupo de diabetes gestacional (13,5 ± 0,5) se redujo significativamente en comparación con los controles (6,75 ± 1,7) (P <0,01). Este estudio reveló que la diabetes gestacional provoca una pérdida en el número de células beta en crías de ratas de 28 y 56 días de edad.

mRNA and Protein levels of rat pancreas specific protein disulphide isomerase are downregulated during Hyperglycemia.

Diabetes (Type I and Type II) which affects nearly every organ in the body is a multi-factorial non-communicable disorder. Hyperglycemia is the most characteristic feature of this disease. Loss of beta cells is common in both types of diabetes whose detailed cellular and molecular mechanisms are yet to be elucidated. As this disease is complex, identification of specific biomarkers for its early detection, management and devising new therapies is challenging. Based on the fact that functionally defective proteins provide the biochemical basis for many diseases, in this study, we tried to identify differentially expressed proteins during hyperglycemia. For that, hyperglycemia was induced in overnight fasted rats by intra-peritoneal injection of streptozotocin (STZ). The pancreas was isolated from control and treated rats for subsequent analyses. The 2D-gel electrophoresis followed by MALDI-TOF-MS-MS analyses revealed several up- and down- regulated proteins in hyperglycemic rat pancreas including the downregulation of a pancreas specific isoform of protein disulphide isomerase a2 (Pdia2).This observation was validated by western blot. Quantitative PCR experiments showed that the level of Pdia2 mRNA is also proportionally reduced in hyperglycemic pancreas.

Reduction of Sulfonylurea with the Initiation of Basal Insulin in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Undergoing Long-Term Sulfonylurea-Based Treatment

BACKGROUND: There were a limited number of studies about β-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of β-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin. METHODS: In this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR). Following a 75-g oral glucose tolerance test (OGTT), we administered long-acting basal insulin to the two groups. After a 6-month follow-up, we repeated the OGTT. RESULTS: Among 69 enrolled patients, 57 completed the study and were analyzed: 31 in the SM and 26 in the SR group. At baseline, there was no significant difference except for the longer duration of diabetes and lower triglycerides in the SR group. After 6 months, the HbA1c was similarly reduced in both groups, but there was little difference in the insulin dose. In addition, insulin secretion during OGTT was significantly increased by 20% to 30% in both groups. A significant weight gain was observed in the SM group only. The insulinogenic index was more significantly improved in the SR group. CONCLUSION: Long-acting basal insulin replacement could improve the glycemic status and restore β-cell function in the T2DM patients undergoing sulfonylurea-based treatment, irrespective of the sulfonylurea dose reduction. The dose reduction of the concurrent sulfonylurea might be beneficial with regard to weight grain.