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

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

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 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.

Objective To investigate the effect of serum CYFRA21-1 and SCCAg levels on the prognosis of patients with cervical cancer radiotherapy.Methods 100 cases of cervical cancer were diagnosed by pathological examination in our hospital from October 2008 and October 2011,Using radioimmunoassay(RIA) in detection of serum CYFRA21-1 and SCCAg level,Pearson and Spearman correlation is used to study the relationship between serum CYFRA21-1 and SCCAg level and cervical cancer patients with clinical features,using the Cox regression model of CYFRA21-1 and SCCAg level and uterine cervix cancer death or recurrence and metastasis of the relationship.Results 100 cases of patients with cervical cancer,endpoint events in 21 cases,LNR4 patients appear higher risk of endpoint events about 44.3%,CYFRA21-1 and SCCAg levels were with cervical cancer patients with CA-125 values,tumor staging,depth of tumor invasion into positive correlation,and the age of patients,no significant correlation,tumor differentiation(P=0.013),serum CYFRA21-1 levels(P=0.02),serum SCCAg levels(P=0.03),depth of tumor invasion(P=0.04) is cervical cancer patients with endpoint events independent risk factors.Conclusion CYFRA21-1 and SCCAg levels were closely related to the prognosis of patients with cervical cancer radiotherapy.

AIM: To investigate the effects of milrinone (a selective phosphdiesterase III inhibitor PDE 3) on insulin secretion, blood glucose, plasma free fatty acids (FFA) and dose-response relationship, and assess possible effects of milrinone on glucose metabolism and insulin sensitivity in conscious rats. METHODS: The catheterized nonstressed rats were administered by the varying doses of milrinone (1, 5, 25 ?mol/kg) and were compared with controls. A hyperinsulinaemic- euglycaemic clamp was established in awake rats, and milrinone(25 ?mol/kg) and 25% dimethyl sulfoxide (DMSO, as a control) were given at 120 min during hyperinsulinaemic- euglycaemic clamp. Glucose turnover was decided by gas chromatograph mass spectrometer (GC-MS). RESULTS: After dosing, plasma FFA levels in 3 milrinone groups significantly increased compared with the controls and before dosing. The percentages of elevation of FFA by the different milrinone doses were very similar, 50%, 52%, 55% for 1, 5, 25 ?mol/kg respectively at 2 min after dosing. Plasma insulin levels were significantly elevated in the 5 and 25 ?mol/kg groups, and the effect of milrinone on glucose concentration was detectable only 25 ?mol/kg group. During hyperinsulinaemic clamp, there were significant increase in plasma FFA (from 173.1?15 2 to 633 8?87 3 ?Eq/L) and hepatic glucose production (HGP), and a significant decrease in glucose infusion rates (GIR) (to about 21%). CONCLUSION: These data suggest that milrinone impaires the abilities of insulin to suppress lipolysis and HGP, and insulin-mediated glucose utilization in peripheral tissue. Therefore, milrinone administration may induce an acute insulin resistance in vivo.

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.

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

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.