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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

1
Howard 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.

PMID:
20638297
PMCID:
PMC3994704
DOI:
10.1016/j.tem.2010.06.005
[Indexed for MEDLINE]
Free PMC Article

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