Anti-diabetes effects and mechanisms of a Chinese herbal medicine preparation JQ-R in diabetic KKAy mice and in vitro / 中国药理学与毒理学杂志

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-1or 200 mg·kg-1BW) 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.

Anti-diabetic effects and mechanisms of action of a Chinese herbal medicine preparation JQ-Rand in diabetic KKmice

Refined-JQ (JQ-R) is a mixture of refined extracts from(Ranunculaceae),(Leguminosae) and(Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KKmice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KKmice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B (NF-B p65), inhibitor of NF-B (IB), c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KKmice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.

Angiotensin Ⅱ and insulin crosstalk in the cardiovascular system / 中南大学学报(医学版)

Under normal physiology, insulin exerts vasodilatory and pro-survival actions via the phosphati dylinositol 3-kinase (PI3-kinase) pathway and vasoconstrictive and mitogenic actions via the mitogen-activated protein kinase (MAPK) pathway in the vasculature. In the insulin resistant states, insulin signals through the PI3-kinase pathway are blunted but its signals through the MAPK cascade remain intact. This imbalance predisposes insulin resistant patients to hypertension and atherosclerosis. The renin-angiotensin system (RAS) is expressed both systemically and locally in the cardiovascular system. Insulin resistance up-regulates the local RAS which contributes to the pathogenesis of hypertension, heart failure, and atherosclerosis. Angiotensin Ⅱ impairs insulin signaling, induces inflammation via the NF-κB pathway, reduces nitric oxide availability and facilitates vasoconstriction,leading to insulin resistance and endothelial dysfunction. Thus the RAS, insulin resistance and inflammation perpetuate each other and coordinately contribute to endothelial dysfunction, vascular injury and atherosclerosis. RAS inhibition decreases cardiovascular and renal morbidity and mortality and the incidence of new onset Type 2 diabetes.