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PLoS Genet. 2011 Dec;7(12):e1002429. doi: 10.1371/journal.pgen.1002429. Epub 2011 Dec 29.

MAPK/ERK signaling regulates insulin sensitivity to control glucose metabolism in Drosophila.

Author information

1
Institute of Molecular and Cell Biology, Singapore, Singapore.

Abstract

The insulin/IGF-activated AKT signaling pathway plays a crucial role in regulating tissue growth and metabolism in multicellular animals. Although core components of the pathway are well defined, less is known about mechanisms that adjust the sensitivity of the pathway to extracellular stimuli. In humans, disturbance in insulin sensitivity leads to impaired clearance of glucose from the blood stream, which is a hallmark of diabetes. Here we present the results of a genetic screen in Drosophila designed to identify regulators of insulin sensitivity in vivo. Components of the MAPK/ERK pathway were identified as modifiers of cellular insulin responsiveness. Insulin resistance was due to downregulation of insulin-like receptor gene expression following persistent MAPK/ERK inhibition. The MAPK/ERK pathway acts via the ETS-1 transcription factor Pointed. This mechanism permits physiological adjustment of insulin sensitivity and subsequent maintenance of circulating glucose at appropriate levels.

PMID:
22242005
PMCID:
PMC3248469
DOI:
10.1371/journal.pgen.1002429
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors have declared that no competing interests exist.

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