This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cheng, C. M. Articles by Bondy, C. A. Search for Related Content PubMed PubMed Citation Articles by Cheng, C. M. Articles by Bondy, C. A.

A Ketogenic Diet Increases Brain Insulin-Like Growth Factor Receptor and Glucose Transporter Gene Expression

Developmental Endocrinology Branch (C.M.C., B.K., J.W., D.S., C.A.B.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; and Department of Biology (D.A.E.), Georgetown University, Washington, DC 20057

Address all correspondence and requests for reprints to: Carolyn A. Bondy, Building 10/10N262, 10 Center Drive, National Institutes of Health, Bethesda, Maryland 20892. E-mail: bondyc{at}mail.nih.gov.

A ketogenic diet suppresses seizure activity in children and in juvenile rats. To investigate whether alteration in brain IGF activity could be involved in the beneficial effects of the ketogenic diet, we examined the effects of this diet on IGF system gene expression in the rat brain. Juvenile rats were fed one of three different diets for 7 d: ad libitum standard rat chow (AL-Std), calorie-restricted standard chow (CR-Std), or a calorie-restricted ketogenic diet (CR-Ket). The calorie-restricted diets contained 90% of the rats’ calculated energy requirements. The AL-Std diet group increased in weight, whereas the two CR groups merely maintained their weight during the 7-d diet. Glucose levels were significantly reduced in both CR groups compared with the AL-Std group, but only the CR-Ket group developed ketonemia. IGF1 mRNA levels were reduced by 30–50% in most brain regions in both CR groups. IGF1 receptor (IGF1R) mRNA levels were decreased in the CR-Std group but were increased in the CR-Ket diet group. Brain IGF binding protein (IGFBP)-2 and -5 mRNA levels were not altered by diet, but IGFBP-3 mRNA levels were markedly increased by the ketogenic diet while not altered by calorie restriction alone. Brain glucose transporter expression was also investigated in this study. Glucose transporter (GLUT) 4 mRNA levels were quite low and not appreciably altered by the different diets. Parenchymal GLUT1 mRNA levels were increased by the CR-Ket diet, but endothelial GLUT1 mRNA levels were not affected. Neuronal GLUT3 expression was decreased with the CR-Std diet and increased with the CR-Ket diet, in parallel with the IGF1R pattern. These observations reveal divergent effects of dietary caloric content and macronutrient composition on brain IGF system and GLUT expression. In addition, the data may be consistent with a role for enhanced IGF1R and GLUT expression in ketogenic diet-induced seizure suppression.

This article has been cited by other articles:

				M. J. Henwood, P. S. Thornton, C. M. Preis, C. Chee, and A. Grimberg Reconciling Diabetes Management and the Ketogenic Diet in a Child with Pyruvate Dehydrogenase Deficiency J Child Neurol, May 1, 2006; 21(5): 436 - 439. [Abstract] [PDF]

				S. Gu, C. J. Villegas, and J. X. Jiang Differential Regulation of Amino Acid Transporter SNAT3 by Insulin in Hepatocytes J. Biol. Chem., July 15, 2005; 280(28): 26055 - 26062. [Abstract] [Full Text] [PDF]