HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/3/E604    most recent 00012.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sonntag, W. E. Articles by Riddle, D. Search for Related Content PubMed PubMed Citation Articles by Sonntag, W. E. Articles by Riddle, D.

Growth hormone and IGF-I modulate local cerebral glucose utilization and ATP levels in a model of adult-onset growth hormone deficiency

Departments of ¹Physiology and Pharmacology and ²Neurobiology and Anatomy, ³Roena Kulynych Center for Memory and Cognition Research, and ⁴Department of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina

Submitted 9 January 2006 ; accepted in final form 20 April 2006

Decreases in plasma IGF-I levels that occur with age have been hypothesized to contribute to the genesis of brain aging. However, support for this hypothesis would be strengthened by evidence that growth hormone (GH)/IGF-I deficiency in young animals produces a phenotype similar to that found in aged animals. As a result, we developed a unique model of adult-onset GH/IGF-I deficiency by using dwarf rats specifically deficient in GH and IGF-I. The deficiency in plasma IGF-I is similar to that observed with age (e.g., 50% decrease), and replacement of GH restores levels of IGF-I to that found in young animals with normal GH levels. The present study employs this model to investigate the effects of circulating GH and IGF-I on local cerebral glucose utilization (LCGU). Analysis of LCGU indicated that GH/IGF-I-deficient animals exhibit a 29% decrease in glucose metabolism in many brain regions, especially those involved in hippocampally dependent processes of learning and memory. Similarly, a high correlation between plasma IGF-I levels and glucose metabolism was found in these areas. The deficiency in LCGU was not associated with alterations in GLUT1, GLUT3, or hexokinase activity. A 15% decrease in ATP levels was also found in hippocampus of GH-deficient animals, providing compelling data that circulating GH and IGF-I have significant effects on the regulation of glucose utilization and energy metabolism in the brain. Furthermore, our results provide important data to support the conclusion that deficiencies in circulating GH/IGF-I contribute to the genesis of brain aging.

insulin-like growth factor I; glucose utilization; brain; adenosine triphosphate; aging

This article has been cited by other articles:

				D. Davila and I. Torres-Aleman Neuronal Death by Oxidative Stress Involves Activation of FOXO3 through a Two-Arm Pathway That Activates Stress Kinases and Attenuates Insulin-like Growth Factor I Signaling Mol. Biol. Cell, May 1, 2008; 19(5): 2014 - 2025. [Abstract] [Full Text] [PDF]