Anti-diabetes effects and mechanisms of a Chinese herbal medicine preparation JQ-R in diabetic KKAy mice and in vitro

OBJECTIVE To investigate the effects and mechanisms by which JQ-R regulated the glucose metabolism and improves insulin sensitivity in diabetic KKAy mice and insulin-resistant L6 myotubes.JQ-R is a mixture of refined extracts from Coptis chinensis,Astragalus membranaceus and Lonicera japonica,three major herbs of JinQi-JiangTang tablet.METHODS Diabetic KKAy mice were adminis.tered JQ-R(100 mg·kg^(-1) or 200 mg·kg^(-1) BW) for 10 weeks.Levels of fasting plasma glucose,lipids,insulin and hemoglobin A1c were monitored.Systemic insulin sensitivity was quantified using the eugly.cemic clamp.The effect of JQ-R on the expressions of the enzymes involved in insulin signaling,oxidative stress and inflammation(Akt,NFκB,IΚBα,JNK,Erk,p38 MAPK) were measured in L6 insulin-resis.tant myotubes.RESULTS JQ-R showed beneficial effects on glucose homeostasis and insulin sensi.tivity in diabetic KKAy mice after 10 weeks treatment.JQ-R also ameliorated the plasma lipid profiles.Moreover,JQ-R can directly reverse the decreased activity of SOD and increased MDA levels as well as activity of iNOS in insulin resistant L6 cell induced with palmitic acid(PA).The expressions of phos.phorylation of NF-κB p65,IκBα,JNK1/2 and Erk1/2 were also decreased after JQ-R treatment.It was also shown that the insulin-stimulated glucose uptake increased significantly after JQ-R treatment,with upregulated expression of phosphorylation of Akt.CONCLUSION JQ-R ameliorated the glucose and lipid metabolism and insulin sensitivity in diabetic KKAy mice.In vitro treatment with JQ-R directly enhanced insulin stimulated glucose uptake in insulin resistant myotubes with improved insulin signal.ling and inflammatory response and oxidative stress state.

Novel N-(pyrimidin-4-yl)thiazol-2-amine derivatives as dual-action hypoglycemic agents that activate GK and PPARc

A series of novel N-(pyrimidin-4-yl)thiazol-2-amine derivatives have been synthesized and evaluated as glucokinase(GK)activators.Ethyl 2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl-amino)thiazole-5-carboxylate was found to be a potent dual-acting hypoglycemic agent activating both GK and PPARg.When given orally to normal mice,the compound demonstrated significant efficacy in decreasing the glucose level after oral glucose loading.

Design, synthesis and metabolic regulation effect of farnesoid X receptor (FXR) antagonistic benzoxepin-5-ones

A series of benzoxepin-5-ones were designed and synthesized by the cyclization of chalcones which were previously found as FXR antagonists. The cellular FXR antagonism of benzoxepines was investigated,among which the most potent compound 10 l was able to reduce the plasma and hepatic triglyceride and plasma ALT levels in mice.