Toward Connecting Metabolism to the Exocytotic Site.

Within cells the regulated exocytosis of secretory granules controls multiple physiological functions, including endocrine hormone secretion. Release of the glucose-regulating hormone insulin from pancreatic islet β cells is critical for whole-body metabolic homeostasis. Impaired insulin secretion appears early in the progression to type 2 diabetes (T2D). Key mechanisms that control the β-cell exocytotic response, mediating the long-known but little understood metabolic amplification of insulin secretion, are becoming clearer. Recent insights indicate a convergence of metabolism-driven signals, such as lipid-derived messengers and redox-dependent deSUMOylation, at the plasma membrane to augment Ca2+-dependent insulin exocytosis. These pathways have important implications for the metabolic control of hormone secretion, for the functional compensation that occurs in obesity, and for impaired insulin secretion in diabetes. Copyright Â