Insulin-like growth factor 1 regulates developing brain glucose metabolism

Clara M. Cheng, Rickey R. Reinhardt, Wei Hua Lee, George Joncas, Sonya C. Patel, Carolyn A. Bondy

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

The brain has enormous anabolic needs during early postnatal development. This study presents multiple lines of evidence showing that endogenous brain insulin-like growth factor 1 (Igf1) serves an essential, insulin-like role in promoting neuronal glucose utilization and growth during this period. Brain 2-deoxy-D- [1-14C]glucose uptake parallels Igf1 expression in wild-type mice and is profoundly reduced in Igf1-/- mice, particularly in those structures where Igf1 is normally most highly expressed. 2-Deoxy-D-[1-14C]glucose is significantly reduced in synaptosomes prepared from Igf1-/- brains, and the deficit is corrected by inclusion of Igf1 in the incubation medium. The serine/threonine kinase Akt/PKB is a major target of insulin-signaling in the regulation of glucose transport via the facilitative glucose transporter (GLUT4) and glycogen synthesis in peripheral tissues. Phosphorylation of Akt and GLUT4 expression are reduced in Igf1-/- neurons. Phosphorylation of glycogen synthase kinase 3β and glycogen accumulation also are reduced in Igf1-/- neurons. These data support the hypothesis that endogenous brain Igf1 serves an anabolic, insulin-like role in developing brain metabolism.

Original languageEnglish (US)
Pages (from-to)10236-10241
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number18
DOIs
StatePublished - Aug 29 2000

Keywords

  • Akt
  • GLUT4
  • Glucose transporter
  • Glycogen synthase kinase
  • Mental retardation

ASJC Scopus subject areas

  • General

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