Isoform-specific requirement for Akt1 in the developmental regulation of cellular metabolism during lactation.

Published

Journal Article

The metabolic demands and synthetic capacity of the lactating mammary gland exceed that of any other tissue, thereby providing a useful paradigm for understanding the developmental regulation of cellular metabolism. By evaluating mice bearing targeted deletions in Akt1 or Akt2, we demonstrate that Akt1 is specifically required for lactating mice to synthesize sufficient quantities of milk to support their offspring. Whereas cellular proliferation, differentiation, and apoptosis are unaffected, loss of Akt1 disrupts the coordinate regulation of metabolic pathways that normally occurs at the onset of lactation. This results in a failure to upregulate glucose uptake, Glut1 surface localization, lipid synthesis, and multiple lipogenic enzymes, as well as a failure to downregulate lipid catabolic enzymes. These findings demonstrate that Akt1 is required in an isoform-specific manner for orchestrating many of the developmental changes in cellular metabolism that occur at the onset of lactation and establish a role for Akt1 in glucose metabolism.

Full Text

Duke Authors

Cited Authors

  • Boxer, RB; Stairs, DB; Dugan, KD; Notarfrancesco, KL; Portocarrero, CP; Keister, BA; Belka, GK; Cho, H; Rathmell, JC; Thompson, CB; Birnbaum, MJ; Chodosh, LA

Published Date

  • December 2006

Published In

Volume / Issue

  • 4 / 6

Start / End Page

  • 475 - 490

PubMed ID

  • 17141631

Pubmed Central ID

  • 17141631

International Standard Serial Number (ISSN)

  • 1550-4131

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2006.10.011

Language

  • eng

Conference Location

  • United States