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.