OBJECTIVETo analyze the changes of patients with type 2 diabetes in different stages in glucagon (GC) and free fatty acid (FFA) in fasting, OGT and L-Arg experiments, and discusses the role of pancreatic alphabeta cells in diabetes pathogenesis by studying the relations among indexes such as glucagon (GC), free fatty acid (FFA) and blood glucose (BG), insulin, insulin homeostasis model (HOMA) and glucose metabolism hormone secretion curve, in order to provide theoretical basis for the treatment of diabetes.

METHODStudy objects were divided into the T2DM group (45 cases), the IGT group (28 cases) and the NGT group (30 cases) for an OGTT experiment and then an L-Arg experiment on the next day. Under the fasting state, their blood glucose (FBG), insulin (F), glucagon (FGC), free fatty acid (FFA) were detected to calculate HOMA-beta, insulin sensitivity index (ISI) and HOMA-IR of different groups. Meanwhile, efforts were made to calculate different time quantum detected in OGTT and L-Arg experiments and area under the curve AUC(BG), AUC(INS) and AUC(GC).

RESULTObvious overall differences were observed in FFA and FGC of the three groups. FGC of each group was negatively correlated with HOMA-beta and ISI. Among all of the 103 study objects, FGC was positively correlated with FBG and HOMA-IR and negatively correlated with HOMA-beta and ISI, with no correlation with FINS; FFA was positively correlated with FBG, HOMA-IR and negatively correlated with FINS, HOMA-beta, ISI. FGC and FFA were positively correlated in the T2DM group and the IGT group, but with no statistical correlation in the NGT group. The sequence of the three study objects was T2DM > IGR > NGT in AUC(GC) in the OGTT experiment and T2DM > IGR > NGT in in AUC(GC) in the L-Arg experiment, with the significant positive correlation between AUC(GC) and AUC(BG) and significant negative correlation with AUC(INS).

CONCLUSIONGlucagon and free fatty acid of T2DM and IGT patients increased, which was positively correlated with blood glucose and HOMA-IR and negatively correlated with INS, HOMA-beta and ISI. The increase in glucagons of T2DM and IGT patients indicated inappropriate secretion of pancreatic alphabeta cells among patients with type 2 diabetes.

Adult ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; metabolism ; Fatty Acids, Nonesterified ; metabolism ; Female ; Glucagon ; blood ; Humans ; Insulin ; secretion ; Islets of Langerhans ; secretion ; Male ; Middle Aged

This study is to evaluate the effects of the metformin (Met) on β cell function of diabetic KKAy mice. Female diabetic KKAy mice selected by insulin tolerance test (ITT) were divided randomly into two groups. Con group was orally administered by gavage with water, Met group with metformin hydrochloride at a dose of 0.2 g x kg(-1) for about 12 weeks. ITT and glucose tolerance tests (OGTT) were determined. Beta cell function was assessed by hyperglycemic clamp. Pancreatic biochemical indicators were tested. The changes of gene and protein expression in the pancreas and islets were also analyzed by Real-Time-PCR and immunostaining. Met significantly improved glucose intolerance and insulin resistance in KKAy mice. Fasting plasma glucose and insulin levels were also decreased. In addition, Met markedly increased glucose infusion rate (GIR) and elevated the Ist phase and maximum insulin secretion during clamp. It showed that Met decreased TG content and iNOS activities and increased Ca(2+) -Mg(2+)-ATPase activity in pancreas. Islets periphery was improved, and down-regulation of glucagon and up-regulated insulin protein expressions were found after Met treatment. Pancreatic mRNA expressions of inflammation factors including TLR4, NF-κB, JNK, IL-6 and TNF-α were down-regulated, p-NF-κB p65 protein levels also down-regulated by Met. And mRNA expressions of ion homeostasis involved in insulin secretion including SERCA2 and Kir6.2 were up-regulated by Met. Met increased SIRT5 expression level in pancreas of KKAy mice under the hyperglycemic clamp. These results indicated that chronic administration of Met regulated pancreatic inflammation generation, ion and hormone homeostasis and improved β cell function of diabetic KKAy mice.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; drug therapy ; Down-Regulation ; Female ; Glucose Tolerance Test ; Homeostasis ; Inflammation ; drug therapy ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; Interleukin-6 ; metabolism ; Metformin ; pharmacology ; Mice ; NF-kappa B ; metabolism ; Pancreas ; drug effects ; Tumor Necrosis Factor-alpha ; metabolism

The aim of this study was to investigate the relationship between somatostatinergic tone (SST) and the size of growth hormone (GH)-producing pituitary tumors. GH levels of 29 patients with newly diagnosed acromegaly were measured using a 75-gram oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), and an octreotide suppression test (OST). Differences between GH levels during the ITT and the OGTT (DeltaGH(IO)), and between the OGTT and the OST at the same time point (DeltaGH(OS)) were compared according to the size of the tumor and the response pattern to the OST. DeltaGH(IO) of macroadenomas (n=22) was non-significantly higher than those of microadenomas while DeltaGH(OS) of macroadenomas were significantly higher than those of microadenomas. According to further analyses of macroadenomas based on the response pattern to the OST, GH levels during the ITT were significantly higher in non-responders. DeltaGH(OS) showed near-significant differences between responders and non-responders. In conclusion, as the size of the pituitary tumor increases, the effect of glucose on SST appears to be attenuated. Macroadenomas that are non-responders to the OST possess a portion of GH secretion exceeding the range of regulation by SST.
Acromegaly/*diagnosis/*pathology ; Adenoma/drug therapy/*pathology ; Adult ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Female ; Glucose Tolerance Test ; Human Growth Hormone/*blood/secretion ; Humans ; Insulin/blood ; Insulin-Like Growth Factor I/analysis ; Male ; Middle Aged ; Octreotide/therapeutic use ; Pituitary Neoplasms/drug therapy/*pathology

OBJECTIVETo investigate the effect of liraglutide on the inflammatory cytokine interleukin-1β (IL-1β) and apoptotic factor caspase-3 expression in the pancreatic islets of OLETF rats with impaired glucose tolerance.

METHODSTwelve-week-old OLETF rats were randomized into 4 groups and received intraperitoneal injections of saline or liraglutide at 50, 100, or 200 µg/kg twice daily for 12 weeks. Eight LETO rats served as the normal control group and received saline injection. After the treatments, the rats were examined for fasting and 30 min plasma insulin during OGTT test, and the expression levels of IL-1β and caspase-3 mRNA and protein in the pancreatic islets were detected by real-time PCR and Western blotting, respectively.

RESULTSCompared with the saline group, liraglutide significantly decreased the expressions of IL-1β and caspase-3 mRNA and protein, and significantly improved the blood glucose, islet β function and early-phase insulin secretion index in OLETF rats.

CONCLUSIONSLiraglutide can improve islet function and glucose metabolism partially by inhibiting islet IL-1β expression to delay or prevent the development of diabetes in OLETF rats.

Animals ; Blood Glucose ; metabolism ; Caspase 3 ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; Glucagon-Like Peptide 1 ; analogs & derivatives ; pharmacology ; Insulin ; secretion ; Interleukin-1beta ; metabolism ; Islets of Langerhans ; metabolism ; Liraglutide ; Male ; Rats ; Rats, Inbred OLETF

The aim of this study was to assess the prevalence of diabetes and to study the effects of excess growth hormone (GH) on insulin sensitivity and beta-cell function in Korean acromegalic patients. One hundred and eighty-four acromegalic patients were analyzed to assess the prevalence of diabetes, and 52 naive acromegalic patients were enrolled in order to analyze insulin sensitivity and insulin secretion. Patients underwent a 75 g oral glucose tolerance test with measurements of GH, glucose, insulin, and C-peptide levels. The insulin sensitivity index and beta-cell function index were calculated and compared according to glucose status. Changes in the insulin sensitivity index and beta-cell function index were evaluated one to two months after surgery. Of the 184 patients, 17.4% were in the normal glucose tolerance (NGT) group, 45.1% were in the pre-diabetic group and 37.5% were in the diabetic group. The insulin sensitivity index (ISI0,120) was significantly higher and the HOMA-IR was lower in the NGT compared to the diabetic group (P = 0.001 and P = 0.037, respectively). The ISI0,120 and disposition index were significantly improved after tumor resection. Our findings suggest that both insulin sensitivity and beta-cell function are improved by tumor resection in acromegalic patients.
Acromegaly/*diagnosis/etiology/metabolism ; Adult ; Asian Continental Ancestry Group ; Blood Glucose/analysis ; C-Peptide/analysis ; Diabetes Mellitus/epidemiology ; Female ; Glucose Tolerance Test ; Human Growth Hormone/secretion ; Humans ; Insulin/blood/secretion ; *Insulin Resistance ; Insulin-Secreting Cells/cytology/*physiology ; Male ; Middle Aged ; Prediabetic State/epidemiology ; Republic of Korea

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.
Adipokines/blood ; Animals ; Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy ; Dietary Supplements ; Dyslipidemias/blood/*drug therapy ; Glucose Tolerance Test ; Hyperglycemia/blood/*drug therapy ; Hypoglycemic Agents/administration & dosage/*pharmacology ; Hypolipidemic Agents/administration & dosage/*pharmacology ; Insulin/physiology/secretion ; Insulin Resistance ; Insulin-Secreting Cells/physiology/secretion ; Leptin/*blood ; Lipid Metabolism/drug effects ; Lipids/blood ; Male ; Organ Specificity ; Rats ; Rats, Long-Evans ; Taurine/administration & dosage/*pharmacology

OBJECTIVETo investigate the secretion patterns of glucose-dependent insulinotropic polypeptide (GIP) after different dietary loads in subjects with normal glucose tolerance (NGT) and their relation to insulin secretion and plasma glucose levels.

METHODSFourteen subjects with normal glucose tolerance underwent 75 g glucose tolerance test(OGTT) followed by mixed meal tolerance test(MMT) one week later. Blood glucose, insulin, and GIP were measured in the fasting state and at 0, 15, 30, 60, 90 and 120 min after glucose load or mixed meal load.

RESULTSThe first peak value of GIP after glucose load occurred at 15 min (45.09∓4.67 pmol/L). After a brief decline, GIP continued to increase till reaching 59.66∓11.73 pmol/L at 120 min after the load. After the mixed meal load, GIP secretion presented with two peaks: the first peak appeared at 15 min (71.69∓14.19 pmol/L) with a level significantly higher than that at 15 min following glucose load (P<0.05), and the second occurred at 90 min (55.35∓13.19 pmol/L). The area under curve of GIP showed no significant difference between the two loads (P>0.05). Compared with glucose load, mixed meal load resulted in an increase of the first GIP peak and an earlier insulin peak (30 min vs 60 min), but a significant decrease of blood glucose at 15 min (P<0.05).

CONCLUSIONCompared with glucose load, mixed meal (containing fat) can strongly stimulate GIP release and cause earlier occurrence of the insulin peak, which might be an important reason for the lower blood glucose after mixed meal.

Adult ; Blood Glucose ; metabolism ; China ; ethnology ; Diet ; Energy Intake ; Female ; Gastric Inhibitory Polypeptide ; secretion ; Glucose Tolerance Test ; Humans ; Insulin ; secretion ; Male ; Middle Aged ; Young Adult

OBJECTIVETo investigate the hypoglycemic action of rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), one of the anthraquinone derivatives isolated from rhubarb, and study its effects on pancreatic beta-cells in db/db mice.

METHODSThirty 4-week-old db/db mice were randomized for an 8-week treatment with intragastric administration of rhein (120 mg/kg, n=15) or placebo (1% natrium cellulose solution, n=15). After the treatment, intraperitoneal glucose tolerance test (IPGTT) was performed and the area under curve (AUC) of insulin levels in IPGTT was calculated to evaluate insulin secretory function. The AUC(INS0-30) was calculated to evaluate the early-phase insulin secretion. Immunohistochemical staining for insulin was performed to estimate the beta-cell mass, and beta-cell apoptosis was detected using TUNEL assay.

RESULTSCompared with the control group, rhein-treated group showed significantly reduced blood glucose concentrations at 0, 30, 60 and 120 min after glucose load with significantly higher insulin levels at 30, 60 and 120 min. The early-phase insulin secretion was also obviously increased. The beta-cell mass was obviously rescued by the 8-week treatment with rhein, which also notably improved the staining intensity of insulin and suppressed beta-cell apoptosis compared with the control.

CONCLUSIONSEarly rhein treatment significantly improves glucose tolerance by restoring the early-phase insulin secretion in db/db mice and inhibiting the apoptosis of the beta-cells, suggesting the potential of rhein as a novel therapeutic agent for type 2 diabetes.

Animals ; Anthraquinones ; pharmacology ; Apoptosis ; drug effects ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Disease Models, Animal ; Hypoglycemic Agents ; pharmacology ; Insulin ; secretion ; Insulin-Secreting Cells ; drug effects ; Male ; Mice

BACKGROUNDBoth repaglinide and gliclazide are insulin secretagogues widely used in the treatment of type 2 diabetes. They stimulate insulin secretion through distinct mechanisms and may benefit patients from different aspects. The present study was to evaluate the effects of repaglinide or gliclazide on glycaemic control, insulin secretion, and lipid profiles in type 2 diabetes patients.

METHODSA total of 47 newly diagnosed type 2 diabetes patients were randomized 1:1 to receive a 4-week treatment with repaglinide or gliclazide. The standard mixed meal tolerance test was performed before and after the treatment. Plasma glucose (PG), insulin concentration, and lipid profiles were measured. The area under insulin concentration curve (AUC(ins)) and the early-phase insulin secretion index (ΔI(30)/ΔG(30)) were calculated.

RESULTSAfter the trial, fasting and postprandial PG and postprandial insulin improved significantly in both groups (P < 0.05). The maximum insulin concentration occurred earlier in the repaglinide group than that in the gliclazide group. AUC(ins) increased in both groups (P < 0.05), but no significant difference was found between groups. ΔI(30)/ΔG(30) increased in both groups (P < 0.05), especially in the repaglinide group (P < 0.05). Triglyceride and total cholesterol decreased significantly in the repaglinide group in some time points, while no significant change was observed in the gliclazide group.

CONCLUSIONSRepaglinide and gliclazide had similar effects on glycaemic control and total insulin secretion, while repaglinide had more effects on improvements in β-cell function and lipid metabolism.

Adult ; Blood Glucose ; drug effects ; Carbamates ; therapeutic use ; Cholesterol ; blood ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; metabolism ; Fasting ; blood ; Female ; Gliclazide ; therapeutic use ; Humans ; Hypoglycemic Agents ; therapeutic use ; Insulin ; secretion ; Male ; Middle Aged ; Piperidines ; therapeutic use ; Postprandial Period ; drug effects ; Treatment Outcome ; Triglycerides ; blood

The purpose of the present study is to investigate the effects of urotensin II (UII) on insulin secretion in islet beta cells and the underlying mechanism. Glucose tolerance test was performed in Wistar rats to evaluate the effect of UII on the levels of plasma glucose and insulin. Static incubation experiment was employed to investigate the effect of UII on glucose-induced insulin secretion (GIIS) in betaTC-6 cells. After the incubation, insulin content and mRNA level in betaTC-6 cells were analyzed. Finally, Western blot was used to find out if UII could change the expression levels of pancreatic duodenal homeobox-1 (PDX-1) and glucokinase (GCK). It was observed that intravenous administration of UII (30, 300 nmol/kg) resulted in a significant decrease in insulin level 15 min after glucose load, and induced an obvious increase in plasma glucose 90 min after the load. In vitro, two hours of UII incubation inhibited GIIS in betaTC-6 cells without affecting insulin content and mRNA levels. The inhibitory effect of UII was blocked by UII receptor antagonist (urantide), and partially blunted by protein kinase C (PKC) inhibitor (chelerythrine) and somatostatin receptor antagonist (cyclosomatostatin). Moreover, we found that GCK protein level was significantly reduced by UII, while PDX-1, a key regulator of insulin gene transcription in beta cells, was not affected. These results suggest that UII-induced inhibition of GIIS in betaTC-6 cells are mediated by UII receptor and PKC pathway, as well as somatostatin receptor which could be activated by high dose of UII. The inhibitory effect of UII on insulin secretion is rather associated with a suppression of GCK expression than a regulation on PDX-1 expression.
Animals ; Blood Glucose ; metabolism ; Cell Line ; Glucokinase ; metabolism ; Homeodomain Proteins ; metabolism ; Insulin ; secretion ; Insulin-Secreting Cells ; metabolism ; physiology ; secretion ; Male ; Mice ; Rats ; Rats, Wistar ; Trans-Activators ; metabolism ; Urotensins ; pharmacology