Physiological and pathological changes in glucose regulate brain Akt and glycogen synthase kinase-3

Buffie Clodfelder-Miller, Patrizia De Sarno, Anna A. Zmijewska, Ling Song, Richard S Jope

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Insulin regulates the phosphorylation and activities of Akt and glycogen synthase kinase-3 (GSK3) in peripheral tissues, but in the brain it is less clear how this signaling pathway is regulated in vivo and whether it is affected by diabetes. We found that Akt and GSK3 are sensitive to glucose, because fasting decreased and glucose administration increased by severalfold the phosphorylation of Akt and GSK3 in the cerebral cortex and hippocampus of non-diabetic mice. Brain Akt and GSK3 phosphorylation also increased after streptozotocin administration (3 days), which increased blood glucose and depleted blood insulin, indicating regulation by glucose availability even with deficient insulin. Changes in Akt and GSK3 phosphorylation and activities in epididymal fat were opposite to those of brain after streptozotocin treatment. Streptozotocin-induced hyperglycemia and increased brain Akt and GSK3 phosphorylation were reversed by lowering blood glucose with insulin administration. Long term hyperglycemia also increased brain Akt and GSK3 phosphorylation, both 4 weeks after streptozotocin and in db/db insulin-resistant mice. Thus, the Akt-GSK3 signaling pathway is regulated in mouse brain in vivo in response to physiological and pathological changes in insulin and glucose.

Original languageEnglish
Pages (from-to)39723-39731
Number of pages9
JournalJournal of Biological Chemistry
Volume280
Issue number48
DOIs
StatePublished - Dec 2 2005
Externally publishedYes

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Glycogen Synthase Kinase 3
Phosphorylation
Brain
Glucose
Insulin
Streptozocin
Hyperglycemia
Blood Glucose
Medical problems
Cerebral Cortex
Fasting
Hippocampus
Blood
Fats
Availability
Tissue

ASJC Scopus subject areas

  • Biochemistry

Cite this

Physiological and pathological changes in glucose regulate brain Akt and glycogen synthase kinase-3. / Clodfelder-Miller, Buffie; De Sarno, Patrizia; Zmijewska, Anna A.; Song, Ling; Jope, Richard S.

In: Journal of Biological Chemistry, Vol. 280, No. 48, 02.12.2005, p. 39723-39731.

Research output: Contribution to journalArticle

Clodfelder-Miller, Buffie ; De Sarno, Patrizia ; Zmijewska, Anna A. ; Song, Ling ; Jope, Richard S. / Physiological and pathological changes in glucose regulate brain Akt and glycogen synthase kinase-3. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 48. pp. 39723-39731.
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