The core autophagy protein ATG5 controls the polarity of the Golgi apparatus and insulin secretion of pancreatic beta cells

Biochem Biophys Res Commun. 2022 Nov 12:629:26-33. doi: 10.1016/j.bbrc.2022.08.084. Epub 2022 Sep 6.

Abstract

Pancreatic beta cells are insulin-producing cells that are structurally and functionally polarized in the islets of Langerhans. The organization and position of the Golgi complex play a key role in maintaining a polarized cell state, but the factors and molecular mechanisms determining the Golgi polarization of pancreatic beta cells are still unknown. In the current study, using pancreatic beta cell-specific Atg5 knockout mice, we found that Atg5, an essential gene for autophagy, plays a pivotal role in regulating Golgi integrity and polarization by affecting the expression of genes involved in vesicle transport. Deletion of Atg5 led to endoplasmic reticulum (ER) stress and impaired the distribution of proinsulin and insulin secretion of pancreatic beta cells, which further exacerbates diabetes. These results contribute to a comprehensive understanding of autophagy-mediated Golgi polarization and its regulation of the function of pancreatic beta cells.

Keywords: Autophagy; Diabetes; Golgi apparatus; Polarity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Autophagy-Related Protein 5 / genetics
  • Autophagy-Related Protein 5 / metabolism
  • Golgi Apparatus / metabolism
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells* / metabolism
  • Mice
  • Mice, Knockout
  • Proinsulin / metabolism

Substances

  • Atg5 protein, mouse
  • Autophagy-Related Protein 5
  • Insulin
  • Proinsulin