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Am J Pathol. 2010 Oct;177(4):1936-45. doi: 10.2353/ajpath.2010.100363. Epub 2010 Sep 2.

Adiponectin lowers glucose production by increasing SOGA.

Author information

1
Departments of Nutrition, School of Medicine and Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

Erratum in

  • Am J Pathol. 2011 Mar;178(3):1406. Cowerd, Rachael B [corrected to Cowherd, Rachael B].

Abstract

Adiponectin is a hormone that lowers glucose production by increasing liver insulin sensitivity. Insulin blocks the generation of biochemical intermediates for glucose production by inhibiting autophagy. However, autophagy is stimulated by an essential mediator of adiponectin action, AMPK. This deadlock led to our hypothesis that adiponectin inhibits autophagy through a novel mediator. Mass spectrometry revealed a novel protein that we call suppressor of glucose by autophagy (SOGA) in adiponectin-treated hepatoma cells. Adiponectin increased SOGA in hepatocytes, and siRNA knockdown of SOGA blocked adiponectin inhibition of glucose production. Furthermore, knockdown of SOGA increased late autophagosome and lysosome staining and the secretion of valine, an amino acid that cannot be synthesized or metabolized by liver cells, suggesting that SOGA inhibits autophagy. SOGA decreased in response to AICAR, an activator of AMPK, and LY294002, an inhibitor of the insulin signaling intermediate, PI3K. AICAR reduction of SOGA was blocked by adiponectin; however, adiponectin did not increase SOGA during PI3K inhibition, suggesting that adiponectin increases SOGA through the insulin signaling pathway. SOGA contains an internal signal peptide that enables the secretion of a circulating fragment of SOGA, providing a surrogate marker for intracellular SOGA levels. Circulating SOGA increased in parallel with adiponectin and insulin activity in both humans and mice. These results suggest that adiponectin-mediated increases in SOGA contribute to the inhibition of glucose production.

PMID:
20813965
PMCID:
PMC2947288
DOI:
10.2353/ajpath.2010.100363
[Indexed for MEDLINE]
Free PMC Article

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