A noncanonical, GSK3-independent pathway controls postprandial hepatic glycogen deposition

Min Wan, Karla F. Leavens, Roger W. Hunter, Shlomit Koren, Alexander Von Wilamowitz-Moellendorff, Mingjian Lu, Santhosh Satapati, Qingwei Chu, Kei Sakamoto, Shawn C. Burgess, Morris J. Birnbaum

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Insulin rapidly suppresses hepatic glucose production and slowly decreases expression of genes encoding gluconeogenic proteins. In this study, we show that an immediate effect of insulin is to redirect newly synthesized glucose-6-phosphate to glycogen without changing the rate of gluconeogenesis. This process requires hepatic Akt2, as revealed by blunted insulin-mediated suppression of glycogenolysis in the perfused mouse liver, elevated hepatic glucose production during a euglycemic-hyperinsulinemic clamp, or diminished glycogen accumulation during clamp or refeeding in mice without hepatic Akt2. Surprisingly, the absence of Akt2 disrupted glycogen metabolism independent of GSK3α and GSK3β phosphorylation, which is thought to be an essential step in the pathway by which insulin regulates glycogen synthesis through Akt. These data show that (1) the immediate action of insulin to suppress hepatic glucose production functions via an Akt2-dependent redirection of glucose-6-phosphate to glycogen, and (2) insulin increases glucose phosphorylation and conversion to glycogen independent of GSK3.

Original languageEnglish (US)
Pages (from-to)99-105
Number of pages7
JournalCell Metabolism
Volume18
Issue number1
DOIs
StatePublished - Jul 2 2013

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Wan, M., Leavens, K. F., Hunter, R. W., Koren, S., Von Wilamowitz-Moellendorff, A., Lu, M., Satapati, S., Chu, Q., Sakamoto, K., Burgess, S. C., & Birnbaum, M. J. (2013). A noncanonical, GSK3-independent pathway controls postprandial hepatic glycogen deposition. Cell Metabolism, 18(1), 99-105. https://doi.org/10.1016/j.cmet.2013.06.001