PPARGC1A gene Thr394Thr G/A polymorphism and its association with type 2 diabetes mellitus and insulin resistance in a Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To examine the association of the Thr394Thr polymorphism of PPARGC1A gene with type 2 diabetes (T2DM), insulin resistance (IR) and other metabolic disorders in a Chinese population.</p><p><b>METHODS</b>Three hundred and seven subjects including 151 T2DM patients and 156 normal glucose tolerant controls (NC) were enrolled in this study. The Thr394Thr G/A polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Glucose, insulin, lipids levels were determined in all subjects. Body mass index (BMI), waist circumferences, index of homeostasis model assessment-insulin resistance (HOMA-IR) and blood pressure were also measured.</p><p><b>RESULTS</b>The diabetic subjects had higher levels of BMI, waist circumferences, blood systolic pressure, triglycerides and lower levels of high density lipoprotein-cholesterol (HDL-C) compared with those of control subjects (P<0.05). About 43.7% (66/151) of the T2DM subjects had the AG genotype, while 37.2% (58/156) in the NC group. The frequency of the A allele was 0.225 in T2DM, and 0.186 in the NC subjects. There were no significant differences either in genotype or allelic distribution of G/A polymorphism between the two groups. In the T2DM group, subjects with AA and GA genotypes had significantly higher levels of HOMA-IR, waist circumferences and lower levels of HDL-C (P<0.05) than those carrying GG genotype. HOMA-IR in subjects with AA and AG were significantly higher than those with GG genotype in both groups.</p><p><b>CONCLUSION</b>The A allele of the Thr394Thr (G-->A) polymorphism of the PPARGC1A gene was associated with insulin resistance, and may be related to central obesity and decreased HDL-C levels in Chinese population. The relationship between this polymorphism and T2DM needs further investigation.</p>

Mesenchymal stem cells transplantation mildly ameliorates experimental diabetic nephropathy in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetic nephropathy is a common complication of diabetes mellitus. This study aimed to explore whether mesenchymal stem cells (MSCs) transplantation could attenuate diabetic nephropathy in experimental diabetic rats.</p><p><b>METHODS</b>Sprague-Dawley rats received a single intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). Diabetic rats were randomized to four groups: diabetes control group (DC), ciclosporin A group (CsA), MSC group, and MSC + CsA group (MSCA). Bone marrow mesenchymal stem cells were cultured, identified and labeled by 5-bromo-2'-deoxyuridine (BrdU) in vitro. Then they were transplanted to diabetic rats via introcardiac infusion. Ciclosporin A was administered daily at 5 mg/kg. At 1, 2, 4, 8 weeks after transplantation, random blood glucose, urine albumin/creatinine ratio (Alb/Cr), endogenous creatinine clearance rate and renal mass index were tested. Renal morphology and labeled cells were examined.</p><p><b>RESULTS</b>Cultured MSCs expressed mesenchymal cell phenotype, and could be multidifferentiated to osteogenic and adipogenic cells. Labeled MSCs could be detected in the kidney of nephropathic rats, mainly in renal interstitium, but they did not propagate after engrafting in kidney. Over the course of the experiment, MSCA group showed a significant decrease in blood glucose compared with MSC group, CsA group and DC group (P < 0.05, respectively). The Alb/Cr in MSCA group and MSC group were significantly lower than CsA group and DC group (P < 0.05). And the Alb/Cr in MSCA group showed a significant decrease compared with MSC group (0.74 vs 0.84, P < 0.05). There was a significant difference in renal mass index between the MSCA group and DC group (5.66 vs 6.37, P < 0.05). No significant difference was found in creatinine clearance rate among 4 groups (P > 0.05). Treatment with MSC + CsA significantly ameliorated the morphology of diabetic kidney.</p><p><b>CONCLUSION</b>MSC could mildly ameliorate diabetic nephropathy by decreasing blood glucose, Alb/Cr ratio and renal mass index.</p>

Role of apoptosis and mitochondrial apoptotic pathway in glucolipotoxicity-induced islet beta-cell dysfunction / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of beta-cell dysfunction induced by glucolipotoxicity in high fat-fed obese rats.</p><p><b>METHODS</b>Eighteen high-fat obese male Wistar rats were assigned into 3 groups and underwent 48-hour infusion through the jugular vein with normal saline (n=6), 20% intralipid + heparin (FFA group, n=6), or 25%glucose +20% intralipid + heparin (GS-FFA group, n=6). The plasma beta-hydroxybutyric acid (beta-HBA) was measured before and at the end of the infusion. After the infusion, the rats were sacrificed following an intravenous glucose tolerance test (IVGTT) to remove the tail of the pancreas for detection of apoptotic islet cells using TUNEL method. Immunohistochemical staining was performed to detect the expression of cytochrome c (cyt c), apoptosis-inducing factor (AIF), caspase-9 and caspase-3 in the islet cells.</p><p><b>RESULTS</b>At the end of the infusion, all the rats exhibited increased plasma beta-HBA levels, which was the highest in the GS-FFA group (P<0.05). IVGTT performed after the infusion showed a significantly lower insulinogenic index in GS-FFA group than that in NS and FFA groups. Greater number of apoptotic islet cells was found in the GS-FFA group than in the FFA and NS groups (P<0.05), and the islets had significantly higher levels of cyt c, AIF, caspase-9 and caspase-3 in the former group than in the latter two groups (P<0.05).</p><p><b>CONCLUSIONS</b>Hyperglycemia and high free fatty acid level synergistically impair insulin secretions to cause ketone overproduction in high fat-fed obese rats. The beta-cell dysfunction due to glucolipotoxicity is associated with increased beta-cell apoptosis and activation of mitochondrial apoptotic pathway.</p>

The associations of HLA-DQB1 gene with onset age and autoantibodies in type 1 diabetes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To evaluate the associations of human leukocyte antigen (HLA) DQB1 gene with onset age and autoantibodies in type 1 diabetes mellitus(T1DM) in Chinese Han population in Sichuan area.</p><p><b>METHODS</b>Forty-six type 1 diabetic patients and 52 healthy control subjects were involved in this study. HLA-DQB1 typing was performed by polymerase chain reaction-sequence specific primer(PCR-SSP). Glutamic acid decarboxylase antibody (GADA) and islet cell antibody (ICA) were qualitatively analyzed by enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The positive rate of DQB1*0201 was higher in T1DM than in controls (OR=18, P<0.005), but those of DQB1*0601, *0602 were higher in controls than in T1DM(OR=0.07, 0.31 respectively, both P<0.05).The positive rate of DQB1*0602 in type 1 diabetic patients with onset age>or=20 years was higher than that in the patients with onset age <20 years (P<0.05). GADA was more frequent in DQB1*0201(+) patients than in DQB1*0201 (-) patients (P<0.025).</p><p><b>CONCLUSION</b>The findings show that DQB1*0201 is susceptible to T1DM, whereas DQB1*0601, *0602 are protective in Chinese Han population in Sichuan area. DQB1*0602 may delay the onset of T1DM. The positive rate of DQB1*0201 correlates positively with that of GADA.</p>

Establishment of perfusion technique for isolated rat pancreas / 中华内分泌代谢杂志

Objective To establish an isolated rat pancreas perfusion technique,a method for the precise measurement of insulin secretion in vitro.Methods An isolated rat pancreas perfusion technique was applied in the study of insulin secretion from?-cells in 10 high-fat diet-induced obese Wistar rats.Results For the assessment of the functional integrity of the perfused pancreas,the isolated pancreas of 6 rats met all the criteria: (1)The constancy of perfusion pressure was kept over the whole experiment time[(70?5)mm Hg,1 mm Hg= 0.133 kPa].(2)The duodenal peristaltic activity of isolated pancreas and duodenum block was present after perfusion experiment.(3)Total insulin response to arginine stimulation was significantly increased as compared with glucose stimulation[maximum insulin secretion rate:(987?100)?U/min vs(545?50)?U/min,P