Diabetes Mellitus, Type 2 ; drug therapy ; Humans ; Hypoglycemic Agents ; therapeutic use ; Non-alcoholic Fatty Liver Disease ; drug therapy

Objective To investigate the role played by fibroblast growth factor-21 (FGF-21) in glucoselipid metabolism in mice adipocyte and hepatocyte. Methods FGF-21 over-expressive vector and FGF-21-shRNA vector were transfected to Hepa1-6 hepatocyte and 3T3-L1 adipocyte, respectively. FGF-21 protein levels were evaluated by Western blotting, glucose uptake rate (GUR) was evaluated by radioimmunoassay. The mRNA expression of transcription factors was detected by real-time quantitative PCR. Results Transfection of pcDNAFGF21 significantly increased FGF-21 expression in both liver and fat cells (4.8 fold and 4.2 fold, both P<0.05). Moreover, FGF-21 expressions were down-regulated by 86. 3% and 77. 8% with pGenesil-FGF21,respectively (both P<0.05 ). The FGF-21 up-regulation markedly increased GUR and decreased intracellular triglycerides content in the 3T3-L1 adipocyte. Meanwhile, the up-regulation of glucose transporter-1, insulin receptor substrate-1 (IRS-1), PPARγ, adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL),and adipocyte fatty acid binding protein 2 ( ap2 ) mRNA expressions were also observed ( all P<0. 05 ). The reverse changes happened in FGF-21 deficient adipocyte except IRS-1. In hepatocyte, FGF-21 has no effect on GUR.FGF-21 over-expression reduced PPARγ, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), and phosphoenolpyruvate carboxykinase (PEPCK) mRNA expressions, and increased low-density lipoprotein receptor expression (P<0.05). Conclusions FGF-21 regulates glucose homeostasis and accommodates intracellular fat content in adipocyte. In hepatocyte, FGF-21 plays an important role in gluconeogenesis and cholesterol metabolism.

Insulin-mediated glucose metabolism of peripheral tissue and liver was assessed by euglycemic hyperinsulinemia clamp technique in lipid-infused rats. There was a significant increase in plasma free fatty acids and a significant reduction in glucose infusion rates in the lipid-infused group. The suppressive effect of insulin on hepatic glucose production (HGP) was significantly blunted and the rate of glucose disappearance showed a slight decrease in the lipid-infused rats, suggesting that lipid impaired the abilities of insulin to suppress lipolysis, HGP and insulin-mediated glucose utilization in peripheral tissues.

Objective To investigate the effects of Liraglutide on plasma FGF-21 level in patients with type 2 diabetes mellitus (T2DM). Methods Enzyme linked immunosorbent assay (ELISA) was used to measure plasma FGF-21 level in patients with T2DM and normal controls (NGT). Relationship between plasma FGF-21level and BMI, WHR, HOMA-IR, HOMA-IS, FFA was analyzed. After Liraglutide treatment, plasma FGF-21level was observed in patients with T2DM. Results Fasting plasma FGF-21 level was higher in T2DM patients than that in normal control group ( 1.81 ±0.32 vs. 1.32 ±0.09 μg/L, P ＜0.01 ). After Liraglutide treatment, WHR, BMI, FPG, 2hPBG, HbA1c and FFA in T2DM patients significantly decreased ( P ＜0.05 or P ＜0. 01 ),HOMA-IS remarkably increased (P ＜ 0. 01 ), and FGF-21 had no change. Conclusion Liraglutide and FGF-21may have different roles in insulin resistance.

Objective To investigate the effects of tumor necrosis factor-alpha (TNF-?) on insulin sensitivity and glucose-lipid metabolism in TNF-?-induced IR mice. Methods Male C57BL/6J mice were given an intraperitoneal injection of TNF-? (H group,6?g/kg; M group,3?g/kg; L group,1?g/kg;twice daily) and saline (NC group) for 7 days. The plasma glucose and insulin were assayed during intravenous glucose tolerance test (IVGTT) and hyperinsulinemic-euglycemic clamp combined with 3-[3H] glucose as a tracer was carried out. Results After TNF-? treatment,fasting blood glucose (FBG),plasma insulin and free fatty acids (FFA) were significantly elevated in H group compared with NC,L and M groups (P

Fasting plasma preptin level was assayed by RIA in the patients with different glucose tolerances. Regarding fasting plasma preptin levels, it was higher in females than in males. Fasting plasma preptin level was increased in patients with type 2 diabetes as compared with subjects of impaired glucose tolerance and normal controls, and there were positive correlations with diastolic blood pressure, blood triglyceride, total cholesterol, high-density lipoprotein-cholesterol, free fatty acids, 2 h plasma glucose after glucose load, HbA1C and HOMA-IR, suggesting a potential link between preptin and glucose-lipid metabolism and insulin resistance.

To evaluate the association of ealpain-10 gene UCSNP-43 polyorphism with type 2 diabetes in Chinese Han population.Meta-analysis showed that calpain-10 gene UCSNP-43 polymorphism may be associated with type 2 diabetes in Chinese Han population.Allele G and genotypo GG may be risk factors for type 2 diabetes,while allele A and genotype GA may be the protective factors.

AIM: To investigate the effects of lipid-induced insulin resistance on plasma resistin and ghrelin levels in awake rats. METHODS: A hyperinsulinaemic-euglycaemic clamp was established in awake chronically catheterized rats. Two groups of rats were studied either with a 4 h intraarterial infusion of lipid/heparin or saline. Insulin-mediated peripheral and hepatic glucose metabolism was assessed by insulin clamp combined with [~3H]-glucose infusion, and plasma resistin and ghrelin concentrations were examined before and after clamp with ELISA. RESULTS: During clamp, there was a significant increase in plasma free fatty acid (FFA, P

The effect of RNA interference-mediated adiponectin gene silence on glucose-lipid metabolism in apolipoprotein E gene knock-out(ApoE~(-/-)) mice was studied. The plasma adiponectin level in ApoE~(-/-) mice with high-fat diet and adiponectin short hairpin RNA (shRNA) adenovirus injection (ADI group) was significantly lower than that in ApoE~(-/-)mice with high-fat diet(HF group), normal-chow(NF group)and naked adenovirus injection (GF, both P<0.01). Fasting blood glucose, fasting plasma insulin, free fatty acids, total cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and body weight were significandy elevated in three high-fat diet groups compared with in NF group, (P<0.01). However, fasting plasma insulin, free fatty acids, total cholesterol, triglycerides, LDL-C, and HDL-C in ADI group were significantly higher than those in HF and GF groups(P<0.01 or P<0. 05). A typical clinical phenotype of glucose-lipid metabolism and insulin resistance in ApoE~(-/-) mice can be induced by high-fat feeding and adiponecting gene silencing.

Objective To investigate the change expression levels of secreted frizzled related protein 5 (SFRP5) mRNA and protein in human adipose,and muscle tissues and the relationship between SFRP5 and insulin resistance in different glucose tolerance subjects.Methods Twelve type 2 diabetes mellitus(T2DM) patients and 12 aged and sex-matched healthy control subjects were enrolled.T2DM patients were diagnosed by1999 WHO criterion.Under the same conditions,the omental adipose and muscle tissues from these patients undergoing elective abdominal surgery were obtained.Expressions of sfrp5 protein and mRNA in adipose and muscle tissues were determined by semi—quantitive RT-PCR and Western blot while body height,weight,waist circumference,hipcircumference,blood pressure,lipodemia,fasting plasma glucose,fasting insulin,glycosylated hemoglobin,fasting serum insulin(FINS),HOMA-β,HOMA-insulin resistance index(HOMA-IR) etc were investigated.Results 1.SBP,TG,FPG,2 h PG,Fins,HOMA-IR,HbA1C were significantly higher in T2DM groups than in the control group.2.The expressions of SFRP5 mRNA and protein in omental adipose tissues were significantly higher inT2DM group than in the control group(P ＜ 0.01).3.The level of SFRP5 mRNA and protein expressions were higher in omental adipose tissue than in the muscle tissues.Conclusions The fact that mRNA and protein expression level of SFRP5 was higher in adipose tissue than in muscle indicates adipose tissue may be the main source of SFRP5.The expressions of SFRP5 mRNA and protein were higher inT2DM group than in the control group indicates sfrp5 may play a role in insulin resistance.