Identification of genes that are differentially expressed in omental fat of normal weight subjects, obese subjects and obese diabetic patients / 中国应用生理学杂志

<p><b>AIM</b>To identify genes that are differentially expressed in omental fat of normal weight subjects, obese subjects and obese type 2 diabetic patients.</p><p><b>METHODS</b>Using a home-made high-density cDNA microarray, we compared gene expression profile of omental fat from normal weigh subjects, obese subjects and obese type 2 diabetic patients, to identify adipose-specific genes associated with obesity and diabetes.</p><p><b>RESULTS</b>119 and 257 genes were up-regulated in obese patients and obese diabetic patients respectively, while 46 and 58 genes were down-regulated in obese patients and obese diabetic patients respectively. 77 genes, including metabolism related genes (PDK4), and caveolin 2, metallo thionein 1B, were up-regulated in both obese and obese diabetic patients, while 8 genes, including key enzymes in lipid synthesis, such as HMG-CoA synthase, fatty acid synthase and stearoyl-CoA desaturase, were down-regulated in both groups. Another interesting finding was that tyrosine-3-monooxygenase/ tryptophan 5-monooxygenase activation protein theta (YWHAZ), a negative regulator for insulin signal transduction, was up-regulated only in obese diabetic patient, but not in normal-glycemic obese subjects.</p><p><b>CONCLUSION</b>Our study demonstrated that decrease of lipogenesis along with increase of fatty acids oxidation of adipose tissue could be a common cause of insulin resistance in obesity and type 2 diabetes, while functional changes of other genes, such as immune regulation genes,might also be involved in the pathogenesis of obesity and type 2 diabetes. Block of insulin signal transduction might trigger the transition from obesity to diabetes. Further exploration of these genes will greatly help us in the understanding of the pathogenesis of obesity and type 2 diabetes.</p>

Role and mechanism of rosiglitazone on the impairment of insulin secretion induced by free fatty acids on isolated rat islets / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prolonged exposure of pancreatic beta-cells to fatty acids increases basal insulin secretion but inhibits glucose-stimulated insulin secretion. Rosiglitazone is a new antidiabetic agent of the thiazolidinediones. However, the relationship between thiazolidinediones and insulin secretion is highly controversial. The aim of this study is to explore the effect and mechanism of rosiglitazone on insulin secretion of islets under chronic exposure to free fatty acids (FFA).</p><p><b>METHODS</b>Pancreatic islets were isolated from the pancreata of male Sprague-Dawley rats by the collagenase digestion and by the dextran gradient centrifugation method. The purified islets were cultured in the presence or absence of rosiglitazone and palmitate for 48 hours. The insulin secretion was measured by radioimmunoassay. The mRNA level of peroxisome proliferator-activated receptor gamma, uncoupling protein 2 (UCP-2) and insulin were determined by real-time polymerase chain reaction (PCR). The cell cytotoxicity assay was measured by cell counting kit-8.</p><p><b>RESULTS</b>Islets exposed to elevated palmitate for 48 hours showed an increased basal and a decreased glucose-stimulated insulin secretion (P < 0.01). The mRNA level of UCP-2 was increased by 3.7 fold in the 0.5 mmol/L concentration of palmitate. When islets were cultured with palmitate (0.5 mmol/L) in the presence of rosiglitazone (1.0 micromol/L), both basal and glucose-stimulated insulin secretion reversed to a pattern of control islets (P < 0.05, P < 0.01). The addition of rosiglitazone in the culture medium decreased the mRNA level of UCP-2 by 2.2 fold, having a statistically significant difference (P < 0.05) as compared with islets cultured with palmitate alone. The cell viability was not affected.</p><p><b>CONCLUSION</b>The protective effects of rosiglitazone on insulin secretion of isolated pancreatic islets under chronic exposure to palmitate might be mediated through the downregulation of UCP-2 expression.</p>

Effect of Amylin on Secretion of Insulin and Glucagon in Rats / 上海第二医科大学学报

Objective To study the effect of amylin on the secretion of glucagon and insulin in isolated rat islets. Methods The models of isolated rat islets were established by collagenase digestion and dextran gradient centrifugation. The influence of various concentrations of amylin on both glucagon and insulin secretion was studied. Results Various concentrations of glucose increased the insulin secretion and decreased the glucagon secretion.Compared with the control, islets exposed to amylin (10~ -10 to 10~ -5 mol/L) for 1 hour showed decreasing glucagon secretion as the glucose increased (0, 5.6 and 11.2 mmol/L) (P

Metabolic Characteristics of Insulin Secretion and Insulin Sensitivity in Isolated Postchallenge Hyperglycemia / 上海第二医科大学学报

Objective To evaluate the metabolic characteristics of insulin secretion and insulin sensitivity in isolated postchallenge hyperglycemia(IPH) and to clarify the factors responsible for the development of IPH. Methods(Eight hundred) and fifty subjects were classified into the following three groups based on the results of a 75-g oral glucose tolerance test(OGTT): normal glucose tolerance(NGT),n=557;isolated impaired glucose tolerance(iIGT),n=146;and IPH,n=147.Insulin secretion(insulinogenic index) and insulin sensitivity(insulin sensitivity index) were identified in the three groups. Results From NGT to iIGT and IPH in these subjects,the insulinogenic index and insulin sensitivity index were gradually decreased(P

Absence of evidence for the association of single nucleotide polymorphisms in Annexin A1 gene with type 2 diabetes in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify single nucleotide polymorphisms (SNPs) in the annexin A1(ANXA1) gene and to analyze the association of these SNPs with type 2 diabetes in Shanghai Han population.</p><p><b>METHODS</b>SNPs in the promotor and exon regions (including intron sequence near splicing site) in the ANXA1 gene were screened by direct sequencing in 24 type 2 diabetes patients and were further genotyped by direct sequencing in another 171 type 2 diabetes patients and 189 normal control subjects.</p><p><b>RESULTS</b>The total sequence of ANXA1 gene is 6798 bp. And 7 SNPs were found; among them, 2 SNPs (-7974 C>T and -7040 G>T) were in promotor region, 3 SNPs in intron regions (+9059 A>G, +9204 C>T, +10486 A>G), 1 SNP in 5'-untranslation region (-6614 A>G) and 1 SNP in coding regions (+1784 A>G). These 7 SNPs were genotyped further and the results revealed that the allele frequencies of these SNPs showed no significant difference between the diabetic and the control groups (P>0.05).</p><p><b>CONCLUSION</b>There is no association of these SNPs in ANXA1 gene with type 2 diabetes in Shanghai Han population.</p>

Detection of a novel glyoxalase in human adipocytes and analysis of its structure and function / 中华内分泌代谢杂志

Objective To identify novel proteins of human adipocytes by proteomic study,and analyze their strueture and function.Methods The expressed proteins of human adipocytes were identified by 2-D electrophoresis and mass spectrometry,and the structure and function of the novel proteins were predicated via bioinforrnatics.Results My027 is a novel protein of human adipocytes identified by 2-D electrophoresis and mass spectrometry.This protein was confirmed by RT-PCR,sequencing,and prokaryotic expression.My027 protein is located in the cytoplasm and has highly conserved structure,indicating that it is an important functional protein. This protein is highly homologous to glyoxalase superfamily with a whole domain of glyoxalase.It shares 96.7% homologous to glycoxalase between 141-253 amino acids and 95.7% homologous to glycoxalaseⅠbetween 144-244 amino acids.Conclusion The results show that protein My027 appears to have the same function as glyoxalaseⅠ.