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

Endocrinology. 2021 Nov 1;162(11):bqab173. doi: 10.1210/endocr/bqab173.

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.

Keywords: beta cell rest; endoplasmic reticulum stress; insulin secretion; pancreatic islet beta cell; unfolded protein response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological / physiology
  • Animals
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum Stress / physiology*
  • Humans
  • Insulin Secretion / physiology*
  • Insulin-Secreting Cells / physiology*
  • Unfolded Protein Response / physiology