GSK-3β在砷致糖代谢紊乱中的作用

Role of GSK-3βin arsenic-induced glucose metabolism disorders

目的探讨GSK-3β在砷致糖代谢紊乱中的作用。方法选择SD雄性大鼠60只,随机等分为6组,C组(空白组)、L组(低砷组)、H组(高砷组)、CN组(空白GSK3抑制剂组)、LN组(低砷GSK3抑制剂组)、HN组(高砷GSK3抑制剂组),通过饮水砷染毒建立砷致糖代谢紊乱模型后,使用GSK-3β抑制剂(15 mg/kg LiCl)进行干预。ELISA检测血清胰岛素的变化情况,RT-PCR检测肝脏组织GSK-3βmRNA表达水平,WB检测肝脏GSK-3β蛋白活性。结果大鼠砷暴露15周,与对照组比较,各染砷组大鼠血糖增加,L和H组大鼠出现胰岛素抵抗;与H组比较,HN组GSK-3βmRNA表达水平降低(P<0.05);与L组比较,LN组大鼠Ser9-GSK-3β蛋白水平增高(P<0.05);与H组比较,HN组大鼠Ser9-GSK-3β蛋白水平增高(P<0.05);与L组比较,LN组GSK3β蛋白活性降低(P<0.05);与H比较,HN组GSK-3β蛋白活性降低(P<0.05)。结论砷可增加GSK-3β蛋白活性,抑制GSK-3β磷酸化,进而发生胰岛素抵抗,血糖升高,导致糖代谢紊乱。

Objective To explore the role of GSK-3βin arsenic-induced disorders of glucose metabolism.Methods Sixty SD male rats were selected and randomly divided into 6 groups,including group C(empty group),group L(low arsenic group),group H(high arsenic group),group CN(white GSK3 inhibitor group),group LN(low arsenic GSK3 inhibitor group)and group HN(high arsenic GSK3 inhibitor group).After drinking arsenic poisoning to establish a pattern of arsenic-induced glucose metabolism disorder,the GSK-3βinhibitor(15 mg/kg LiCl)was used for surgery.Serum insulin in was detected by ELISA.RT-PCR was used to detect GSK-3βmRNA expression level in liver tissue and GSK-3βprotein activity in liver was detected by Western blot assay.Results Rats were exposed to arsenic for 15 weeks.Compared to group C,the blood glucose in the arsenic-exposed groups increased and rats in the L and H groups developed insulin resistance.Compared with group H,the expression level of GSK-3βmRNA in group HN was reduced.Compared to group L,the level of Ser9-GSK-3βprotein in group LN increased.Compared to group H,the level of Ser9-GSK-3βprotein increased in group HN.Compared with group L,GSK-3βprotein activity in group LN decreased.Compared to group H,GSK3βprotein activity in group HN was decreased.Conclusion Arsenic enhances the activity of the GSK-3βprotein and inhibits GSK-3βphosphorylation and induces insulin resistance and increases blood sugar and finally causes the glucose metabolism disorders.