黄芪多糖对KKAy小鼠骨骼肌蛋白激酶B丝氨酸磷酸化的影响

目的:观察胰岛素刺激下蛋白激酶B(PKB)丝氨酸磷酸化水平在遗传性2型糖尿病小鼠(KKAy)骨骼肌组织的变化及黄芪多糖(APS)对其影响。方法:选取雌性KKAy16只,随机分为2组:糖尿病组和糖尿病黄芪多糖治疗组;选取雌性C57BL/6J小鼠20只作为对照组,随机分为正常对照组和黄芪多糖对照组。于黄芪多糖治疗前后观察体重、血糖、血胰岛素水平、胰岛素抵抗指数及口服葡萄糖耐量试验,治疗8周后用免疫印迹法检测骨骼肌组织胰岛素刺激的丝氨酸磷酸化PKB表达。结果:KKAy小鼠体重、血糖及胰岛素抵抗指数均显著高于C57BL/6J组,同时伴有明显的糖耐量异常(P<0.01),经APS治疗8周后,各项实验指标均明显降低(P<0.01)。KKAy小鼠骨骼肌组织胰岛素刺激的丝氨酸磷酸化PKB表达水平显著低于C57BL/6J小鼠(P<0.01),黄芪多糖可明显提高KKAy小鼠骨骼肌丝氨酸磷酸化PKB表达(P<0.05),但对C57BL/6J小鼠各项指标无显著影响。结论:胰岛素刺激下的PKB磷酸化障碍是2型糖尿病胰岛素抵抗的重要机制之一,黄芪多糖可增强胰岛素刺激的丝氨酸磷酸化PKB表达水平,从而改善KKAy小鼠胰岛素抵抗。

Effect of Astragalus Polysaccharide on Ser Phosphorylation of Protein Kinase B in Skeletal Muscle of KKAy Mice

Objective: To examine potential effects of astragalus polysaccharide (APS) treatment on glucose homeostasis and protein kinase B(PKB) Ser473 phosphorylation in skeletal muscle in vivo from KKAy diabetic mice and C57BL/6J non-diabetic mice. Methods: Female KKAy (age eight weeks, n=16) and C57BL/6J mice(age eight weeks, n=20)were respectively randomized to the APS treated and control groups. In the groups with APS, KKAy and C57BL/6J mice were administered with APS\700 mg/(kg·d)\] from the age of 12 weeks and lasted for eight weeks. Body weight, blood glucose level, plasma insulin concentration,insulin resistance index and oral glucose tolerance test(OGTT) were observed pre-and post-APS therapy. At the end of eight-weeks treatment with APS, the insulin stimulated serine phosphorylation of serine/threonine protein kinase B in skeletal muscle was assessed. Results: Compared with C57BL/6J mice, there were significant increases in body weight, blood glucose level and insulin resistance index, and marked impaired in oral glucose tolerance test in KKAy mice(all P<0.01) which were alleviated by treatment with APS for eight weeks(all P< 0.01). Insulin stimulated serine phosphorylation of PKB was lower in KKAy compared to C57BL/6J (P<0.01)and was enhanced in APS treated KKAy mice(P<0.05). While the above changes didn’t occurred in C57BL/6J mice treated with APS. Conclusion: These data implicate decreased insulin stimulated PKB/Akt kinase phosphorylation as an important component underlying insulin resistance in skeletal muscle from KKAy mice. APS treatment attenuated hyperglycaemia with an increased PKB phosphorylation in KKAy mice.