In this review, we focus on recent developments in our understanding of nutrient-induced insulin secretion that challenge a key aspect of the “canonical” model, in which an oxidative phosphorylation-driven rise in ATP production closes K_ATP channels. We discuss the importance of intrinsic β cell metabolic oscillations; the phasic alignment of relevant metabolic cycles, shuttles, and shunts; and how their temporal and compartmental relationships align with the triggering phase or the secretory phase of pulsatile insulin secretion. Metabolic signaling components are assigned regulatory, effectory, and/or homeostatic roles vis-à-vis their contribution to glucose sensing, signal transmission, and resetting the system. Taken together, these functions provide a framework for understanding how allostery, anaplerosis, and oxidative metabolism are integrated into the oscillatory behavior of the secretory pathway. By incorporating these temporal as well as newly discovered spatial aspects of β cell metabolism, we propose a much-refined Mito_Cat-Mito_Ox model of the signaling process for the field to evaluate.

在这篇综述中，我们重点关注我们对营养诱导的胰岛素分泌理解的最新进展，这些进展挑战了“规范”模型的一个关键方面，在该模型中，氧化磷酸化驱动的 ATP 生成增加会关闭 K _ATP渠道。我们讨论了内在 β 细胞代谢振荡的重要性；相关代谢周期、穿梭和分流的阶段性调整；以及它们的时间和区室关系如何与脉动胰岛素分泌的触发阶段或分泌阶段保持一致。代谢信号成分因其对葡萄糖传感、信号传输和重置系统的贡献而被赋予调节、效应和/或稳态作用。总而言之，这些功能为理解变构、回补和氧化代谢如何整合到分泌途径的振荡行为中提供了一个框架。通过结合 β 细胞代谢的这些时间以及新发现的空间方面，我们提出了一种更加精致的 Mito _Cat -Mito_{信令过程的Ox}模型可供现场评估。