Analysis of mechanism of triphenyltin-induced diabetic action : ATP and cAMP related system

单剂量口服三苯基氯化锡（TPT） （60 mg/kg体wt）诱导仓鼠胰岛素分泌减少，诱发糖尿病。三苯基锡诱导的鼠糖尿病发病机制涉及1)葡萄糖诱导的[Ca^<2+>]_i和胰岛素分泌减少，以响应ATP敏感的K^+通道依赖性去极化，这与胰岛细胞NADPH和ATP或ATP/ADP比值的降低有关；2)胰岛细胞中通过pka依赖性和pka非依赖性机制，葡萄糖依赖性胰岛素性多肽（GIP）和胰高血糖素样肽-1 （GLP-1）诱导的Na^+依赖性细胞Ca^<2+>反应的减少（参考文献1）。三苯基锡诱导高K^+和妥布酰胺诱导的[Ca^<2+>]_i和胰岛素分泌增加，增加atp敏感的K^+通道不依赖的胰岛细胞胰岛素分泌。

Oral administration of a single dose of triphenyltin chloride (TPT) (60 mg/kg body wt) induces diabetes with decreased insulin secretion in hamsters.The pathogenesis of triphenyltin-induced diabetes in hamster involves 1) the glucose-induced reduction of [Ca^<2+>]_i and insulin secretion in response to ATP-sensitive K^+ channel-dependent depolarization, which is related to the decrease of NADPH and ATP or ATP/ADP ratio in pancreatic islet cells, 2) the reduction of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1)-induced Na^+-dependent cellular Ca^<2+> response through PKA-dependent and PKA-independent mechanisms in pancreatic islet cells (Ref. 1). Triphenyltin induces the increase of high K^+ and torbutamide-induced [Ca^<2+>]_i and insulin secretion and increases the ATP-sensitive K^+ channel-independent insulin secretion in islet cells.