Kalwat, Michael A.Scheuner, DonalynRodrigues-dos-Santos, KarinaEizirik, Decio L.Cobb, Melanie H.2023-03-092023-03-092021-11Kalwat MA, Scheuner D, Rodrigues-Dos-Santos K, Eizirik DL, Cobb MH. The Pancreatic ß-cell Response to Secretory Demands and Adaption to Stress. Endocrinology. 2021;162(11):bqab173. doi:10.1210/endocr/bqab173https://hdl.handle.net/1805/31779Pancreatic β cells dedicate much of their protein translation capacity to producing insulin to maintain glucose homeostasis. In response to increased secretory demand, β cells can compensate by increasing insulin production capability even in the face of protracted peripheral insulin resistance. The ability to amplify insulin secretion in response to hyperglycemia is a critical facet of β-cell function, and the exact mechanisms by which this occurs have been studied for decades. To adapt to the constant and fast-changing demands for insulin production, β cells use the unfolded protein response of the endoplasmic reticulum. Failure of these compensatory mechanisms contributes to both type 1 and 2 diabetes. Additionally, studies in which β cells are "rested" by reducing endogenous insulin demand have shown promise as a therapeutic strategy that could be applied more broadly. Here, we review recent findings in β cells pertaining to the metabolic amplifying pathway, the unfolded protein response, and potential advances in therapeutics based on β-cell rest.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalBeta cell restEndoplasmic reticulum stressInsulin secretionPancreatic islet beta cellUnfolded protein responseArticle