Diabetes is characterized by elevation of plasma glucose due to an insufficiency of the hormone insulin and is associated with both inadequate insulin secretion and impaired insulin action. The Banting Medal for Scientific Achievement Commemorates the work of Sir Frederick Banting, a member of the team that first used insulin to treat a patient with diabetes almost exactly one hundred years ago on 11 January 1922. This article is based on my Banting lecture of 2022 and concerns the mechanism of glucose-stimulated insulin secretion from pancreatic β-cells, with an emphasis on the metabolic regulation of the KATP channel. This channel plays a central role in insulin release. Its closure in response to metabolically generated changes in the intracellular concentrations of ATP and MgADP stimulates β-cell electrical activity and insulin granule exocytosis. Activating mutations in KATP channel genes that impair the ability of the channel to respond to ATP give rise to neonatal diabetes. Impaired KATP channel regulation may also play a role in type 2 diabetes. I conjecture that KATP channel closure in response to glucose is reduced because of impaired glucose metabolism, which fails to generate a sufficient increase in ATP. Consequently, glucose-stimulated β-cell electrical activity is less. As ATP is also required for insulin granule exocytosis, both reduced exocytosis and less β-cell electrical activity may contribute to the reduction in insulin secretion. I emphasize that what follows is not a definitive review of the topic but a personal account of the contribution of my team to the field that is based on my Banting lecture.

中文翻译：

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KATP 通道以及健康和疾病中胰岛素分泌的代谢调节：2022 年班廷科学成就奖讲座


糖尿病的特征是由于胰岛素激素不足而导致血浆葡萄糖升高，并且与胰岛素分泌不足和胰岛素作用受损有关。班廷科学成就奖章旨在纪念弗雷德里克·班廷爵士 (Sir Frederick Banting) 的工作，他是团队成员，他在大约一百年前的 1922 年 1 月 11 日首次使用胰岛素治疗糖尿病患者。本文基于我 2022 年在班廷的演讲并关注葡萄糖刺激胰腺 β 细胞分泌胰岛素的机​​制，重点是 KATP 通道的代谢调节。该通道在胰岛素释放中起着核心作用。它响应细胞内 ATP 和 MgADP 浓度的代谢变化而关闭，刺激 β 细胞电活动和胰岛素颗粒胞吐作用。 KATP 通道基因的激活突变会损害该通道响应 ATP 的能力，从而导致新生儿糖尿病。 KATP 通道调节受损也可能在 2 型糖尿病中发挥作用。我推测，由于葡萄糖代谢受损，无法产生足够的 ATP 增加，因此响应葡萄糖的 KATP 通道关闭减少。因此，葡萄糖刺激的 β 细胞电活动较少。由于胰岛素颗粒胞吐作用也需要 ATP，因此胞吐作用的减少和 β 细胞电活动的减少可能会导致胰岛素分泌的减少。我强调，接下来的内容并不是对该主题的明确回顾，而是基于我的班廷讲座对我的团队对该领域的贡献的个人描述。