Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Trends Endocrinol Metab. 2010 Oct;21(10):589-98. doi: 10.1016/j.tem.2010.06.005. Epub 2010 Jul 16.

Insulin signaling meets mitochondria in metabolism.

Author information

  • 1Howard Hughes Medical Institute, Division of Endocrinology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.

Abstract

Insulin controls nutrient and metabolic homeostasis via the IRS-PI3K-AKT signaling cascade that targets FOXO1 and mTOR. Mitochondria, as the prime metabolic platform, malfunction during insulin resistance in metabolic diseases. However, the molecular link between insulin resistance and mitochondrial dysfunction remains undefined. Here we review recent studies on insulin action and the mechanistic association with mitochondrial metabolism. These studies suggest that insulin signaling underpins mitochondrial electron transport chain integrity and activity by suppressing FOXO1/HMOX1 and maintaining the NAD(+)/NADH ratio, the mediator of the SIRT1/PGC1α pathway for mitochondrial biogenesis and function. Mitochondria generate moderately reactive oxygen species (ROS) and enhance insulin sensitivity upon redox regulation of protein tyrosine phosphatase and insulin receptor. However, chronic exposure to high ROS levels could alter mitochondrial function and thereby cause insulin resistance.

Copyright © 2010. Published by Elsevier Ltd.

PMID:
20638297
[PubMed - indexed for MEDLINE]
PMCID:
PMC3994704
Free PMC Article

Images from this publication.See all images (4)Free text

Figure 1
Figure 2
Figure 3
Figure 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk