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

139 Citations (Scopus)

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
StatePublished - Aug 29 2000
Externally publishedYes

Fingerprint

Somatomedins
Glucose
Brain
Insulin
Glycogen
Phosphorylation
Glycogen Synthase Kinase 3
Neurons
Facilitative Glucose Transport Proteins
Synaptosomes
Protein-Serine-Threonine Kinases
Growth

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Cheng, C. M., Reinhardt, R. R., Lee, W. H., Joncas, G., Patel, S. C., & Bondy, C. A. (2000). Insulin-like growth factor 1 regulates developing brain glucose metabolism. Proceedings of the National Academy of Sciences of the United States of America, 97(18), 10236-10241.

Insulin-like growth factor 1 regulates developing brain glucose metabolism. / Cheng, Clara M.; Reinhardt, Rickey R.; Lee, Wei Hua; Joncas, George; Patel, Sonya C.; Bondy, Carolyn A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 18, 29.08.2000, p. 10236-10241.

Research output: Contribution to journalArticle

Cheng, CM, Reinhardt, RR, Lee, WH, Joncas, G, Patel, SC & Bondy, CA 2000, 'Insulin-like growth factor 1 regulates developing brain glucose metabolism', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 18, pp. 10236-10241.
Cheng, Clara M. ; Reinhardt, Rickey R. ; Lee, Wei Hua ; Joncas, George ; Patel, Sonya C. ; Bondy, Carolyn A. / Insulin-like growth factor 1 regulates developing brain glucose metabolism. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 18. pp. 10236-10241.
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