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

三苯基锡诱导糖尿病作用的机制分析：ATP和cAMP相关系统

• 批准号: 16590480
• 负责人: MIURA Yoshikazu
• 金额: $ 1.98万
• 依托单位: Dokkyo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590480/
• 关键词: Triphenyltin; Insulin secretion; Cytosolic Ca^<2+>; Cytosolic Na^+; Membrane potential; ATP; ADP ratio; NADPH; Hamster; AChレセプター; GLPレセプター; SUR1; 糖尿病; インクレチン; ジアゾキシド; 高K^+; ADP

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.

口服单剂量氯化三苯基锡（TPT）三苯基锡（60 mg/kg体重）诱导仓鼠糖尿病伴胰岛素分泌减少，其发病机制包括：1）葡萄糖诱导的ATP敏感性K^+通道依赖性去极化引起的[Ca^<2+>]_i和胰岛素分泌减少，其与胰岛细胞中NADPH和ATP或ATP/ADP比值降低有关，2）葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽-1（GLP-1）诱导的Na^+依赖性细胞Ca^<2+>反应通过PKA依赖性和PKA-1途径降低，胰岛细胞中的独立机制（参考文献1）。三苯基锡可诱导高钾和托丁胺诱导的胰岛细胞[Ca^2+] i和胰岛素分泌增加，并可增加ATP敏感性K^+通道非依赖性胰岛素分泌。

项目成果

Triphenyltin impairs a protein kinase A (PKA)-dependent increase of cytosolic Na+ and Ca2+ and PKA-independent increase of cytosolic Ca2+ associated with insulin secretion in hamster pancreatic β-cells

• DOI: 10.1016/j.taap.2006.05.017
• 发表时间: 2006-11-01
• 期刊: TOXICOLOGY AND APPLIED PHARMACOLOGY
• 影响因子: 3.8
• 作者: Miura, Yoshikazu;Matsui, Hisao
• 通讯作者: Matsui, Hisao

Triphenyltin impairs a protein kinase A (PKA)-dependent increase of cytosolic Na^+ and PKA-independent increase of cytosolic Ca^<2+> associated with insulin secretion in hamster pancreatic β-cells

三苯基锡损害与仓鼠胰腺 β 细胞胰岛素分泌相关的蛋白激酶 A (PKA) 依赖性胞质 Na^+ 增加和 PKA 独立的胞质 Ca^2+ 增加

• 发表时间: 2006
• 期刊: Toxicology and Applied Pharmacology 216
• 作者: Yoshikazu Miura;Hisao Matsui
• 通讯作者: Hisao Matsui