Format

Send to

Choose Destination
See comment in PubMed Commons below
Diabetes. 2015 Jan;64(1):147-57. doi: 10.2337/db13-1715. Epub 2014 Aug 4.

PTEN deletion in pancreatic α-cells protects against high-fat diet-induced hyperglucagonemia and insulin resistance.

Author information

  • 1Toronto General Research Institute, University Health Network, Toronto, ON, Canada Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
  • 2Toronto General Research Institute, University Health Network, Toronto, ON, Canada Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
  • 3Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
  • 4Department of Physiology, University of Toronto, Toronto, ON, Canada.
  • 5Toronto General Research Institute, University Health Network, Toronto, ON, Canada Institute of Medical Science, University of Toronto, Toronto, ON, Canada Division of Endocrinology & Metabolism, Department of Medicine, University Health Network, Toronto, ON, Canada mwoo@uhnresearch.ca.

Abstract

An aberrant increase in circulating catabolic hormone glucagon contributes to type 2 diabetes pathogenesis. However, mechanisms regulating glucagon secretion and α-cell mass are not well understood. In this study, we aimed to demonstrate that phosphatidylinositol 3-kinase (PI3K) signaling is an important regulator of α-cell function. Mice with deletion of PTEN, a negative regulator of this pathway, in α-cells show reduced circulating glucagon levels and attenuated l-arginine-stimulated glucagon secretion both in vivo and in vitro. This hypoglucagonemic state is maintained after high-fat-diet feeding, leading to reduced expression of hepatic glycogenolytic and gluconeogenic genes. These beneficial effects protected high-fat diet-fed mice against hyperglycemia and insulin resistance. The data demonstrate an inhibitory role of PI3K signaling on α-cell function and provide experimental evidence for enhancing α-cell PI3K signaling for diabetes treatment.

© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk