Autophagy Differentially Regulates Insulin Production and Insulin Sensitivity.

ABSTRACT: Autophagy, a stress-induced lysosomal degradative pathway, has been assumed to exert similar metabolic effects in different organs. Here, we establish a model where autophagy plays different roles in insulin-producing β cells versus insulin-responsive cells, utilizing knockin (Becn1^F121A) mice manifesting constitutively active autophagy. With a high-fat-diet challenge, the autophagy-hyperactive mice unexpectedly show impaired glucose tolerance, but improved insulin sensitivity, compared to mice with normal autophagy. Autophagy hyperactivation enhances insulin signaling, via suppressing ER stress in insulin-responsive cells, but decreases insulin secretion by selectively sequestrating and degrading insulin granule vesicles in β cells, a process we term "vesicophagy." The reductio

SUBMITTER: Yamamoto S 

PROVIDER: S-EPMC6054876 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature