Insulin granules. Insulin secretory granules control autophagy in pancreatic β cells

Science. 2015 Feb 20;347(6224):878-82. doi: 10.1126/science.aaa2628.


Pancreatic β cells lower insulin release in response to nutrient depletion. The question of whether starved β cells induce macroautophagy, a predominant mechanism maintaining energy homeostasis, remains poorly explored. We found that, in contrast to many mammalian cells, macroautophagy in pancreatic β cells was suppressed upon starvation. Instead, starved β cells induced lysosomal degradation of nascent secretory insulin granules, which was controlled by protein kinase D (PKD), a key player in secretory granule biogenesis. Starvation-induced nascent granule degradation triggered lysosomal recruitment and activation of mechanistic target of rapamycin that suppressed macroautophagy. Switching from macroautophagy to insulin granule degradation was important to keep insulin secretion low upon fasting. Thus, β cells use a PKD-dependent mechanism to adapt to nutrient availability and couple autophagy flux to secretory function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Cells, Cultured
  • Fasting
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / physiology*
  • Insulin-Secreting Cells / ultrastructure
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase 13 / genetics
  • Protein Kinase C / physiology
  • Secretory Vesicles / metabolism
  • Secretory Vesicles / physiology*


  • Insulin
  • Mitogen-Activated Protein Kinase 13
  • protein kinase D
  • Protein Kinase C