Abstract:Sustained hyperglycemia is the basic feature of insulin resistance and type 2 diabetes. Disorders of glucose homeostasis lead to metabolic dysfunction, thus provoking diabetes and diabetic complications. Sirtuin 1 (Sirt1), a mammalian NAD-dependent protein deacetylase, plays a critical role in energy metabolism and insulin resistance. Recent studies suggest that activation of Sirt1 deacetylates various proteins such as PGC-1α, NF-κB, Foxo1 and Akt, which in turn protects pancreatic β cell functions, improves insulin sensitivity, attenuates inflammation and subsequently maintains glucose homeostasis. This review summarizes recent advances in the role of Sirt1 in regulating glucose homeostasis.

Abstract:Aim To investigate the effect of Neu-P11, a novel melatonin receptor agonist, on insulin sensitivity in sleep restricted rats as well as the underlying mechanism. Methods Method of rotating cage was adopted to establish SD rat models of sleep restriction. During the 8 days of sleep restriction, rats were injected intraperitoneally with Neu-P11 （20 mg/kg）, MLT （5 mg/kg）, saline respectively every day. Plasma glucose, fasting insulin, malondialdehyde （MDA） levels and enzyme activity of glutathione peroxidase （GSH-Px）, superoxide dismutase （SOD） were detected at the end of experiment, the proteins of JNK and phosphorylated JNK in muscles were measured by Western blot. Results Compared with control group, sleep restricted rats showed increased levels of plasma glucose, fasting insulin, but antioxidative potency decreased. However, in Neu-P11 and melatonin-treated sleep restricted rats, the levels of plasma glucose, fasting insulin and MDA decreased with an increase of SOD, GSH-Px activities. Neu-P11 or melatonin also down-regulated the levels of JNK and phosphorylated JNK which were increased by sleep restriction. These data suggest that glucose homeostasis and antioxidative potency of the chronic sleep restricted rats were protected by Neu-P11 and melatonin. Conclusions Neu-P11 could improve metabolic profiles and insulin resistant induced by sleep restriction, and the regulation of JNK and antioxidative potency may be the underlying mechanism.

Abstract:Aim To investigate the inhibiting effect of 17-β estradiol on insulin resistance induced by the high fructose diet in ovariectomized rats. Methods Thirty six ovariectomized female Sprague-Dawley(S-D)rats were fed with the high fructose diet for eight weeks to induce insulin resistance. Then they were randomly divided into three groups: the model group, the 17-β estradiol replacement group,the vehicle control group.The normal control group twelve rats were fed with the normal diet for eight weeks.Body weight(BW),systolic blood pressure(SBP),glucose tolerance,plasma triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDLC)and low density lipoprotein cholesterol(LDLC),fasting blood sugar(FBS)and fasting serum insulin(FSI)and insulin sensitivity index(ISI)were measured. Results Compared with the normal control group,BW(p<0.05),SBP(p<0.05), the levels of plasma TG,TC,LDLC,FBS(all p<0.05) and FSI(p<0.01) were increased significantly and the plasma HDLC level was decreased significantly (p<0.05) in the model group. Glucose tolerance was decreased significantly(p<0.05)and injury of pancreatic β-cell was observed in the model group.ISI was decreased significantly(p<0.05) and insulin resistance was arisesed in the model group.Compared with the model group,these effects were reversed, ISI was increased significantly(p<0.05) and insulin resistance was inhibited in the 17-β estradiol replacement group. Conclusion 17-β estradiol inhibited insulin resistance,injury of pancreatic β-cell and lipid dysbolism induced by the high fructose diet in ovariectomized rats.These findings suggested that estradiol in female rat might provide protection againt the effect of the high fructose diet,which caused hypertension,insulin resistance,injury of pancreatic β-cell and lipid dysbolism.