葡萄糖激酶激动剂对胰岛α细胞胰升糖素分泌的影响

目的 探讨葡萄糖激酶激动剂(GKA)对胰岛α细胞胰升糖素分泌的影响. 方法 (1)αTC1-9细胞株采用0,0.1及1 μmol/L的GKA处理,原代胰岛细胞用0,0.5及1 μmol/L的GKA处理,时间均为1 h,检测低糖刺激的细胞胰升糖素的分泌变化.(2)灌胃法给予SD大鼠0,3及30 mg/kg的GKA处理,分别观察0,15,30,60及120 min时SD大鼠体内血糖、血浆胰升糖素及胰岛素的变化. 结果 (1)αTC1-9细胞株经1 μmol/L的GKA作用1 h后,可显著降低低糖刺激的胰升糖素分泌,比对照组下降了45.16％.(2)原代胰岛细胞经0.5及1 μmol/L的GKA作用1 h后,可显著降低低糖刺激的胰升糖素分泌,分别比对照组下降了68.7％和84.3％.(3)GKA可剂量依赖性地降低SD大鼠的血糖水平,并可刺激大鼠体内胰岛素分泌;3及30 mg/kg的GKA可显著抑制SD大鼠体内的胰升糖素水平. 结论 GKA可抑制胰岛α细胞胰升糖素的分泌,从而改善糖代谢.

Effect of Glucokinase Activators on α-cell Glucagon Secretion

Objective To investigate the effect of glucokinase activators(GKA) on α-cell glucagon releasing.Methods (1) αTC1-9, an α cell line, were incubated with different concentration of GKA(0, 0.1, 1 μmol/L)for 1 h,then the secretion of glucagon stimulated by low glucose were measured.(2) Primary islets were incubated with different concentrations of GKA(0, 0.5, 1 μmol/L)for 1 h,then the secretion of glucagon stimulated by low glucose were measured.(3) SD rats were treated with different concentrations of GKA by intragastric administration, then the blood glucose, plasma glucagon and plasma insulin were detected.Results (1) Exposure of αTC1-9 to GKA(1 μmol/L)for 1 h resulted in a reduction of glucagon secretion, and compared with control group it was reduced by 45.16％.(2) After treated with GKA (0.5, 1 μmol/L)for 1 h,the levels of glucagon in both groups of primary islets were reduced significantly, and compared with control group it was reduced by 68.7％ and 84.3％, respectively.(3) The reduction effect of GKA on blood glucose in SD rats was dose dependent.In both the low dose treatment group(GKA 3 mg/kg)and high dose treatment group(GKA 30 mg/kg), plasma glucagon levels were significantly reduced.GKA stimulated insulin secretion in SD rats.Conclusion GKA may improve glucometabolism, which may be due to the inhibition of glucagon secretion.