The Pancreatic ß-cell Response to Secretory Demands and Adaption to Stress

Michael Kalwat, Donalyn Scheuner, Karina Rodrigues-Dos-Santos, Decio L. Eizirik, Melanie H. Cobb

Research output: Contribution to journalArticlepeer-review

Abstract

Pancreatic 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.

Original languageEnglish (US)
JournalEndocrinology
Volume162
Issue number11
DOIs
StatePublished - Nov 1 2021

Keywords

  • beta cell rest
  • endoplasmic reticulum stress
  • insulin secretion
  • pancreatic islet beta cell
  • unfolded protein response

ASJC Scopus subject areas

  • Endocrinology

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