Disrupting actin filaments enhances glucose-stimulated insulin secretion independent of the cortical actin cytoskeleton

J Biol Chem. 2023 Nov;299(11):105334. doi: 10.1016/j.jbc.2023.105334. Epub 2023 Oct 10.

Abstract

Just under the plasma membrane of most animal cells lies a dense meshwork of actin filaments called the cortical cytoskeleton. In insulin-secreting pancreatic β cells, a long-standing model posits that the cortical actin layer primarily acts to restrict access of insulin granules to the plasma membrane. Here we test this model and find that stimulating β cells with pro-secretory stimuli (glucose and/or KCl) has little impact on the cortical actin layer. Chemical perturbations of actin polymerization, by either disrupting or enhancing filamentation, dramatically enhance glucose-stimulated insulin secretion. Using scanning electron microscopy, we directly visualize the cortical cytoskeleton, allowing us to validate the effect of these filament-disrupting chemicals. We find the state of the cortical actin layer does not correlate with levels of insulin secretion, suggesting filament disruptors act on insulin secretion independently of the cortical cytoskeleton.

Keywords: F-actin; beta cell; cell cortex; depolymerization; hormone secretion; islet of Langerhans; pancreatic islet; polymerization.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Cytoskeleton* / metabolism
  • Actins* / metabolism
  • Animals
  • Glucose / pharmacology
  • Insulin / metabolism
  • Insulin Secretion*
  • Insulin-Secreting Cells* / metabolism

Substances

  • Actins
  • Glucose
  • Insulin