The mechanism of glucose-induced time-dependent potentiation of insulin secretion from pancreatic β cells and its alteration in diabetic state

葡萄糖诱导胰腺β细胞胰岛素分泌时间依赖性增强的机制及其在糖尿病状态下的改变

• 批准号: 13671186
• 负责人: FUJIMOTO Shimpei
• 金额: $ 1.34万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671186/
• 关键词: pancreatic islet; pancreatic β cell; insulin secretion; glucose; priming effect; exocytotic system; intracellular Ca^<2+> concentration; intracelluar ATP concentration; ブドウ島

A brief exposure to elevated glucose augments the insulin secretory response of islets to subsequent stimulation. The site of this time-dependent potentiation (priming effect) of glucose in the mechanism of the regulation of insulin secretion is not completely known, however. Insulin release triggered by a depolarizing concentration of K^+ in the presence of basal glucose is markedly enhanced in primed rat islets. To clarify the role of priming on Ca^<2+> and ATP efficacy in the exocytotic apparatus, islets were electrically permeabilized to vary the intracellular Ca^<2+> and ATP concentration according to the extracellular medium, and insulin release was evaluated. Ca^<2+ >and ATP efficacy in Ca^<2+> and ATP-dependent insulin secretion was not affected by priming, and alteration of the intracellular Ca^<2+> concentration after depolarization cannot account for the phenomenon. There was no difference in ATP content before depolarization between nonprimed and primed islets. Moreover, the decline in ATP level after depolarization with basal glucose was observed in both primed and nonprimed islets. However, a reduced decline in ATP level in the early phase was observed in primed islets. In addition, oligomycin, a mitochondrial metabolism inhibitor, abolished the difference in ATP level between primed and nonprimed islets, suggesting that mitochondrial ATP production may be linked to the phenomenon

短暂暴露于升高的葡萄糖会增强胰岛对随后刺激的胰岛素分泌反应。然而，葡萄糖在胰岛素分泌调节机制中的这种时间依赖性增强（启动效应）的位点尚不完全清楚。在基础葡萄糖存在下，由去极化浓度的K^+触发的胰岛素释放在引发的大鼠胰岛中显着增强。为了阐明胞吐装置中启动对Ca 2+ 和ATP功效的作用，对胰岛进行电透化以根据细胞外介质改变细胞内Ca 2+ 和ATP浓度，并评估胰岛素释放。 Ca ^ 2+ 和Ca ^ 2+ 中的ATP功效和ATP依赖性胰岛素分泌不受启动影响，并且去极化后细胞内Ca ^ 2+ 浓度的改变不能解释该现象。未引发和引发的胰岛去极化前 ATP 含量没有差异。此外，在用基础葡萄糖去极化后，在引发和未引发的胰岛中都观察到 ATP 水平下降。然而，在引发的胰岛中观察到早期阶段 ATP 水平下降幅度较小。此外，寡霉素（一种线粒体代谢抑制剂）消除了引发和未引发的胰岛之间 ATP 水平的差异，表明线粒体 ATP 的产生可能与该现象有关

项目成果

Shen ZJ et al.(7名 4番): "Recovery of function and mass of endogenous beta-cells in streptozotocin-induced diabetic rats treated with islet transplantation"Diabetes Res Clin Pract. 53・1. 9-16 (2001)

Shen ZJ 等（7 人，第 4 期）：“用胰岛移植治疗链脲佐菌素诱导的糖尿病大鼠的功能和质量的恢复”糖尿病研究 53・1（2001 年）。 ）

Kajikawa M, Fujimoto S et al.: "Ouabain suppresses glucose-induced mitochondrial ATP production and insulin release by generating reactive oxygen species in pancreatic islets"Diabetes. 51(8). 2522-2529 (2002)

Kajikawa M、Fujimoto S 等人：“哇巴因通过在胰岛中产生活性氧来抑制葡萄糖诱导的线粒体 ATP 产生和胰岛素释放”糖尿病。

Miyawaki K, Fujimoto S et al.: "Inhibition of gastric inhibitory polypeptide signaiing prevents obesity"Nature Medicine. 8(7). 738-742 (2002)

Miyawaki K、Fujimoto S 等人：“抑制胃抑制性多肽信号传导可预防肥胖”《自然医学》。

Fujimoto S et al.: "Prior exposure to high glucose augments depolarization-induced insulin release by mitigating the decline of ATP level in rat islets"Endocrinology. 143(1). 213-221 (2002)

Fujimoto S 等人：“预先暴露于高葡萄糖可通过减轻大鼠胰岛中 ATP 水平的下降来增强去极化诱导的胰岛素释放”内分泌学。

Takeda T, Tsuura Y, Fujita J, Fujimoto S et al.: "Heat shock restores insulin secretion after injury by nitric oxide by maintaining glucokinase activity in rat islets"Biochem Biophys Res Commun. 284(1). 20-25 (2001)

Takeda T、Tsuura Y、Fujita J、Fujimoto S 等人：“热休克通过维持大鼠胰岛中的葡萄糖激酶活性来恢复一氧化氮损伤后的胰岛素分泌”Biochem Biophys Res Commun。