KATP deficiency in hyperinsulinism and diabetes

项目摘要 这个联合项目的长期目标是了解电子技术的机制、作用和意义。 高胰岛素血症和糖尿病患者胰岛素分泌的控制。以前的努力证明了 KATP通道在胰岛β细胞中的电活动及揭示通道活性如何缺陷 会对胰岛素分泌产生深远影响，并导致高胰岛素血症和新生儿糖尿病。这 现在的理解是分别使用KATP通道激活剂和抑制剂作为第一线 治疗。然而，一种矛盾的，本质上无法解释的，跨越到葡萄糖不足，或直接 糖尿病，在动物和患有高胰岛素血症的人类中都可见。在2型糖尿病中，来自 最初的高分泌到分泌衰竭，可能反映出类似的进展。拟议的研究将利用小说 诱导型KATP通道敲除模型和2型糖尿病模型的综合探讨 这一逆转的机制基础，从而改善对HI和其他形式的HI的理解和管理 长期的细胞分泌衰竭。

Project Summary The long-term goals of this joint project are to understand the mechanisms, role and significance of electrical control of insulin secretion in hyperinsulinism and diabetes. Previous efforts demonstrated the central role of the KATP channel in electrical activity of the pancreatic beta-cell and revealed how defective channel activity can have profound effects on insulin secretion, and cause hyperinsulinism and neonatal diabetes. This understanding now underlies the use of KATP channel activators and inhibitors, respectively, as first line therapies. However, a paradoxical, essentially unexplained, crossover to glucose-insufficiency, or outright diabetes, is seen in both animals and humans with hyperinsulinism. In Type 2 diabetes, a parallel crossover from initial hypersecretion to secretory failure, may reflect a similar progression. Proposed studies will utilize novel inducible KATP channel knockdown models and models of type 2 diabetes to comprehensively probe the mechanistic basis of this reversal, and thereby improve understanding and management of HI and other forms of long-term -cell secretory failure.