METABOLIC OSCILLATIONS AND INSULIN SECRETION

代谢波动和胰岛素分泌

• 批准号: 2389445
• 负责人: KEITH TORNHEIM
• 金额: $ 31.49万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-15 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2389445
• 关键词: 6 phosphofructokinase; Adenoviridae; adenosine diphosphate; adenosine triphosphate; antisense nucleic acid; calcium flux; disease /disorder model; electroporation; enzyme activity; gene expression; glycolysis; insulin; isozymes; laboratory rat; microinjections; noninsulin dependent diabetes mellitus; northern blottings; nucleotide metabolism; pancreatic islet function; pancreatic islets; pathologic process; transfection; western blottings

DESCRIPTION (Adapted from applicant's abstract): The objective of this project is to test the importance of oscillatory B-cell metabolism in insulin secretion, and to examine whether diminution of glycolytic oscillations, due to altered PFK isoform expression or regulation, may be responsible for the diminished insulin oscillations seen in islets from the GK rat, a non-obese model of NIDDM, and in islets from high fat/sucrose-fed (HFHS) Wistar rats. The specific aims are to determine (i) how interference with oscillatory glycolysis affects the rise in the ATP/ADP ratio and the Ca2+ and insulin secretory response of the B-cell; (ii) whether other metabolizable secretagogues (e.g., glyceraldehyde or leucine plus glutamine) stimulate oscillatory insulin secretion by effects on oscillatory glycolysis and the ATP/ADP ratio or whether their metabolism is also intrinsically oscillatory, (iii) whether GK and HFHS Wistar islets have altered PFK isoform expression and kinetics and/or changes in the levels of regulatory metabolites that could account for diminished oscillations; (iv) whether a different magnitude or time course of rise in the ATP/ADP ratio occurs in GK and HFHS Wistar islets on glucose stimulation; (v) whether the diminished oscillations in insulin secretion in a population of GK or HFHS Wistar islets are due to a loss of synchrony.

描述（改编自申请人的摘要）：此目的 项目是测试振荡B细胞代谢的重要性 胰岛素分泌，并检查糖酵解的降低 由于PFK同工型表达或调节，振荡可能是 负责从胰岛中看到的胰岛素振荡减少 GK大鼠，NIDDM的非肥胖模型，在高脂/蔗糖喂养的胰岛中 （HFHS）Wistar大鼠。 具体目的是确定（i）干扰 振荡性糖酵解会影响ATP/ADP比的上升和 B细胞的Ca2+和胰岛素分泌反应； （ii）是否其他 可代谢的促分子（例如，甘油醛或亮氨酸加谷氨酰胺） 通过对振荡性糖酵解的影响刺激振荡性胰岛素分泌 以及ATP/ADP比或它们的代谢是否本质上也是 振荡，（iii）GK和HFHS Wistar胰岛是否改变了PFK 同工型表达和动力学和/或调节水平的变化 可以解释振荡减少的代谢产物； （iv）是否a ATP/ADP比的不同幅度或时间过程发生在GK中 HFHS Wistar胰岛在葡萄糖刺激上； （v）是否减少 GK或HFHS Wistar人群中胰岛素分泌的振荡 胰岛是由于同步损失所致。