摘要
探讨4-羟基肉桂酰胺(4-Hy)作为胰岛素受体增敏剂在糖尿病动物模型上的降糖作用.采用STZ诱导胰岛素缺陷型小鼠模型,对小鼠随机分组:对照组、胰岛素治疗组(Insulin,1U/kg)、不同剂量4-羟基肉桂酰胺治疗组(2.5、5mg/kg)、联合给药组(4-Hy2.5 mg/kg+Insulin组、4-Hy5 mg/kg+Insulin组).对照组小鼠等体积DMSO给药;测定小鼠血糖浓度和血清中胰岛素、胰高血糖素、C肱水平,组织中相关信号通路的表达,基因mRNA的表达水平.结果表明:4-Hy与胰岛素联用能显著延长胰岛素的降血糖效果(p＜0.001);降低了小鼠血清中的平均C肱水平和胰高血糖素水平;在小鼠组织中,4-Hy与胰岛素联用组的p-IR1150/1151及p-AKT(Ser473)表达显著增强(p＜0.01);在肝脏组织中,4-Hy与胰岛素联用组的糖异生水平显著降低(p＜0.001),糖原合成及糖原分解水平显著提高(p＜0.01).说明4-羟基肉桂酰胺作为胰岛素受体的增敏剂可以显著增强胰岛素的降血糖效应.
Abstract
To investigate the hypoglycemic effect of 4-hydroxycinnamamide(4-Hy),an insulin receptor sensitizer,in an animal model of diabetes.The STZ-induced insulin-deficient mouse model was used,and the mice were randomly grouped into the fol-lowing groups:control group,insulin treatment group(1 U/kg),different doses of 4-hydroxycinnamamide treatment group(2.5 and 5 mg/kg),and coadministration group(4-Hy2.5 mg/kg+insulin group and 4-Hy5 mg/kg+insulin group).In the control group,the mice were given an equal volume of the DMSO,blood glucose concentrations,serum insulin,glucagon,and C-peptide levels,the expression of related signaling pathway components in tissues,and the expression levels of the genes.The results showed that the combination of 4-Hy and insulin significantly prolonged the hypoglycemic effect of insulin(p＜0.001)and reduced the average C-peptide and glucagon levels in the serum of mice;in mouse tissues,and the expression of p-IR1 150/1151 and p-AKT(Ser473)was significantly enhanced in the group treated with the combination of 4-Hy and insulin(p＜0.01).In liver tissues,the expression of 4-Hy and insulin was significantly enhanced(p＜0.01).Gluconeogenesis was strongly reduced(p＜0.001),and glycogen synthe-sis and glycogenolysis were significantly increased(p＜0.01)in the 4-Hy and insulin combination group.These findings indicate that 4-hydroxycinnamamide,a sensitizer of insulin receptors,can significantly enhance the hypoglycemic effect of insulin.
基金项目
国家自然科学基金(81760667)
云南省农业联合专项面上项目(202301BD070001-097)
维普
万方数据