Replication of association study between type 2 diabetes mellitus and IGF2BP2 in Han Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The association between IGF2BP2 and type 2 diabetes mellitus (T2DM) has been repeatedly confirmed among different ethnic populations. However, in several genome-wide association studies (GWAS) from the Chinese Han population, the gene IGF2BP2 has not been replicated. The results of relevant studies for the association between IGF2BP2 and T2DM showed controversy in Chinese Han population. It is necessary to systematically evaluate the contribution of common variants in IGF2BP2 to T2DM in Chinese Han population.</p><p><b>METHODS</b>Two single-nucleotide polymorphisms (SNPs, rs4402960 and rs1470579) in IGF2BP2 were genotyped in Chinese Han population (3807 controls/4531 T2DM cases) by Illumina GoldenGate Indexing assay. The association between SNPs and T2DM was evaluated by multiple Logistic Regression analysis. A meta-analysis was used to estimate the effects of IGF2BP2 in 20854 Chinese Han individuals.</p><p><b>RESULTS</b>rs1470579 and rs4402960 were confirmed to have strong association with T2DM in the Chinese Han population (rs1470579 P = 1.80×10(-7), OR (95% CI) = 1.22 (1.14-1.32), rs4402960 P = 7.46×10(-9), OR (95% CI) = 1.26 (1.17-1.37), respectively). Moreover, 11 studies for rs4402960 were included in the meta-analysis and 7 studies for rs1470579. The meta-analysis also showed the association between T2DM and IGF2BP2 (rs1470579 OR of 1.15 (95% CI = 1.10-1.19), P < 0.0001 under an additive model and rs4402960 OR of 1.14 (95% CI = 1.10-1.18), P < 0.0001 under an additive model).</p><p><b>CONCLUSION</b>IGF2BP2 was strongly associated with the risk of T2DM in Chinese Han population.</p>

Role and mechanism of uncoupling protein 2 on the fatty acid-induced dysfunction of pancreatic alpha cells in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Uncoupling protein (UCP) 2 is related to the dysfunction of beta cells induced by fatty acids. However, whether UCP2 has similar effects on alpha cell is still not clear. This study aimed to investigate the effects of UCP2 and its possible mechanisms in lipotoxicity-induced dysfunction of pancreatic alpha cells.</p><p><b>METHODS</b>The alpha TC1-6 cells were used in this study to evaluate the effects of palmitate and/or UCP2 inhibit factors on the glucagon secretory function, glucagon content, the glucagon mRNA level and the nitrotyrosine level in the supernatant. Meantime, the expression levels of UCP2 and peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1 alpha) were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Furthermore, the possible relationship between UCP2 and insulin signal transduction pathway was analyzed.</p><p><b>RESULTS</b>Palmitate stimulated alpha cell glucagon secretion and the expression of UCP2 and PGC-1 alpha, which could be partially decreased by the inhibition of UCP2. Palmitate increased nitrotyrosine level and suppressed insulin signal transduction pathway in alpha cells. Inhibition of UCP2 influenced the effects of free fatty acid on alpha cells and may relate to glucagon secretion.</p><p><b>CONCLUSION</b>UCP2 played an important role on alpha cell dysfunction induced by free fatty acid in vitro, which may be related to its effects on oxidative stress and insulin signal transduction pathway.</p>

Sequence of fat partitioning and its relationship with whole body insulin resistance / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Currently it is unclear whether lipid accumulation occurs in a particular sequence and its relationship with whole body insulin resistance (IR). This study aimed to answer this question.</p><p><b>METHODS</b>Male Sprague-Dawley (SD) rats were fed on a normal or a high-fat diet for 20 weeks. Serum triglycerides (TG), serum free fatty acids (FFA), fasting plasma glucose (FPG), and liver and skeletal muscle TG were measured. The glucose infusion rate (GIR) and mRNA levels of acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase-1 (CPT-1) in the liver and skeletal muscle were determined at different stages.</p><p><b>RESULTS</b>Compared with rats fed on the normal diet, serum FFA was not significantly increased in rats fed on the high-fat diet until 20 weeks. In contrast, liver TG was significantly increased by the high-fat diet by four weeks (20-fold; P < 0.01), and remained elevated until the end of the study. However, skeletal muscle TG was not significantly increased by the high-fat diet until 20 weeks (10.6-fold; P < 0.01), and neither was the FPG. The GIR was significantly reduced (1.6-fold; P < 0.01) by the high-fat diet after 8 weeks. The mRNA levels of ACC gradually increased over time and CPT-1 decreased over time, in both the liver and skeletal muscle in rats fed the high-fat diet.</p><p><b>CONCLUSIONS</b>Lipid accumulation in the liver occurs earlier than lipid accumulation in the skeletal muscle. Fatty liver may be one of the early markers of whole body IR. Changes in the gene expression levels of ACC and CPT-1 may have important roles in the process of IR development.</p>

Relationship between oxidative stress and beta cell lipoapoptosis in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of beta cell lipoapoptosis after long term high-fat feeding in rats, and to investigate the relationship between oxidative stress, gene expression and beta cell lipoapoptosis.</p><p><b>METHODS</b>Forty-one SD male rats were randomly divided into 2 groups: high-fat diet group (HF group) and control group (NC group). At the end of 28 weeks, the levels of malondialdehyde (MDA) and glutamylcysteinylglycine (GSH) in plasma and pancreatic tissue,the early-phase insulin secretion in beta cells, the beta cell apoptosis (TUNEL technology) and the uncoupling protein 2 (UCP2) gene expression in islets were measured.</p><p><b>RESULT</b>The concentrations of MDA both in plasma and pancreatic tissue were higher in HF group than those in NC group.In contrast, The contents of GSH both in plasma and pancreatic tissue were lower in HF group. Insulin secretion response to glucose load was significantly decreased in HF group (3.0 fold Compared with 5.7 fold, P<0.01). Blood glucose levels at 3 min, 5 min and 10 min during IVGTT were significantly higher in HF group than those in NC group (P<0.05). The frequency of beta cell apoptosis was increased by 40.0% in HF group (P<0.01). The gene expression of UCP2 in islets was increased by 22.4% in HF group (P<0.01).</p><p><b>CONCLUSION</b>The frequency of beta cell apoptosis in high-fat feeding rats is affected by oxidative stress, which results in increasing UCP2 gene expression.</p>

Blood pressure reduction found in subjects after evolution of impaired glucose tolerance to normal glucose tolerance or diabetes——New information from The Da-Qing IGT and Diabetes Study / 中华内分泌代谢杂志

Objective To investigate the blood pressure change in relation to the evolution of impaired glucose tolerance (IGT). Methods From 1986 to 1992, 334 subjects with IGT were randomized to placebo, diet, exercise and diet plus exercise intervention groups. No anti-hypertension drug was given to these enrolled subjects. Blood pressure was measured at the beginning and the end of the six-year prospective study. In this analysis these subjects were stratified to seven subgroups based on 2 h plasma glucose (2hPG) level during OGTT at the end of the study: < 7.8,7.8~8.8,8.9~9.9,10.0~11.0,11.1~13.8,13.9~16.6 and≥16.7mmol/L. Blood pressure changes in relation to the evolution of glucose tolerance in these subgroups were compared by least square mean procedure. Results Changes of systolic blood pressure (SBP) in average in these seven groups were -2.4,0.6,7.7,4.3,1.7,-2.9and-6.9mm Hg (1mm Hg=0.133kPa), and changes of diastolic blood pressure (DBP) were-3.2,3.0,3.3,1.7,-0.7,-1.3 and-3.7mm Hg respectively after controlling for age, sex, BMI at baseline and Δ BMI during the follow-up period. In those subjects with IGT evolved into normal glucose tolerance (NGT) or diabetes, reductions in SBP and DBP were significantly greater than those who retained IGT with 2hPG between 8.9-9.9mmol/L (all P < 0.05 ). In 264 out of the 334 subjects with IGT and blood pressure≥130/80mm Hg at baseline, blood pressure changed more strikingly: changes of SBP in these groups were-5.2,-2.6,5.2,2.3,-2.3,-4.2,-7.6mm Hg, and DBP were -5.0, -3.7,1.5, -2.9, -4.3, - 4.0 and-6.0mm Hg respectively after the adjustment of age, sex, BMI, BMI variation. The reductions of SBP and DBP in subjects whose status of IGT was converted to NGT or diabetes were significantly greater than those with retained IGT and 2hPG between 8.9-9.9mmol/L. Conclusion Blood pressure is increased in the subjects with IGT who retained in the IGT group during the six-year follow-up period in Da-Qing Study. On the contrary, subjects with IGT evolved into NGT or diabetes demonstrate significant reduction of blood pressure.

Study on the distribution and risk factors of hypertension among children: a cohort study / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the association between hypertension and the tendency of change among children,so as to lay a foundation for the prevention and control of hypertension.</p><p><b>METHODS</b>Based on findings from the prevalence survey that carried out in September 1999 in Daqing of Heilongjiang province. New admission children were selected as subjects to conduct a five-year cohort study. All the subjects were interviewed with questionnaires and their blood specimens were collected for biochemical analysis. All data were analyzed using SPSS 10.0 software. Results The prevalence of hypertension among 447 children was found 2.01% at the baseline study but increased to 5.37% in the fifth year. During a five year period, the systolic pressure level among children increased from (100.65 +/- 11.62)mmHg (1 mm Hg = 0.133 kPa) to (106.67 +/- 9.29) mm Hg,while the diastolic pressure level was from (66.27 +/- 11.31) mm Hg to (70.28 +/- 7.98) mm Hg and showed significant difference between boys and girls. There were association between hypertension and family history, body mass index (BMI), triglyceride, insulin, insulin resistance index while insulin sensitivity index and family history, BMI and insulin sensitivity index appeared to be the important factors. Children under this study were divided to 'with family history or without' and then every group was divided to 'with over weight-obesity or normal'. Obesity and insulin sensitivity seemed the key risk factors on hypertension. Descent of insulin sensitivity was an independent risk factor.</p><p><b>CONCLUSION</b>The level of blood tension among children in Daqing city was higher than that from the national data. The present study confirmed that over-weight,obesity, heredity and insulin resistance were the risk factors of hypertension while insulin resistance was related to hypertension. The interaction of these risk factors was independent or correlated to each other.</p>

Relationship between hepatic insulin resistance and the expression of genes involved in hepatic glucose output / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the relationship between hepatic insulin resistance induced by high fat diet and the expression of genes involving hepatic glucose output.</p><p><b>METHODS</b>Normal 8-week-old male SD rats were randomly divided into two groups, i.e, normal chow group (NC, n = 10) and high fat diet group (HF, n = 10). They were fed for 28 weeks. Body weight and fasting blood glucose (FBG) were measured. At the end of the experiment, the rats were sacrificed and their fasting insulin (INS) and triglycerides (TG) were measured. Hepatic insulin sensitivity was measured by tissue uptake of 3H-2-deoxyglucose and the content of hepatic glycogen was measured using the anthrone method. Gene expression was investigated by using the semi-quantitative RT-PCR method.</p><p><b>RESULTS</b>As compared with NC group, CF group rats developed visceral obesity which was accompanied by higher plasma TG. FBG in CF group increased starting from the 18th week (NC 4.77+/-63 mmol/L vs HF 5.45+/-87 mmol/L, P < 0.05). The rate of uptake of 3H-2-deoxyglucose in livers decreased by 51% in the HF group. The content of hepatic glycogen increased by 92.4% (P < 0.01). The level of phosphoenolpyruvate carboxykinase (PEPCK) and PGC-1a mRNA increased by 41.5% and 30.8%, respectively (P < 0.05).</p><p><b>CONCLUSION</b>A high fat diet induced expressions of PGC-1a and PEPCK. It suggests that gluconeogenesis may play a role in the increase of hepatic glucose output and FBG.</p>

The sequence of fat deposit and its relationship with insulin resistance / 中华内分泌代谢杂志

Objective To observe the sequence of fat deposit and its relationship with insulin resistance in SD rats fed by high fat diet.Methods Normal 8-week-old male SD rats were randomly divided into normal chow (NC,n=40)and high fat diet(HF,n=40)groups.Triglyceride(TG)in serum,liver and muscle were measured;glucose infusion rate(GIR)and the mRNA level of genes related to lipid metabolism in liver and muscle were determined in different stages.GIR was detected by eugiyeemic-hyperinsulinemic clamp for evaluating the insulin sensitivity.Gene expression was determined by real-time PCR.Results(1)As compared with NC group,serum TG was not increased after high fat feeding for4 and 8 weeks,it began to increase after 12 weeks [0.52(0.15-1.00) mmol/L vs O.31(0.09-0.53)retool/L, P0.05)in skeletal muscle.After 8 weeks,the expression of ACC1 in liver in HF group was increased by 20.6%,CPT-1 was decreased by 27.1%(P