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: 288/5/E973    most recent 00549.2004v1 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 ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by McClain, D. A. Articles by Cooksey, R. C. Search for Related Content PubMed PubMed Citation Articles by McClain, D. A. Articles by Cooksey, R. C.

Adipocytes with increased hexosamine flux exhibit insulin resistance, increased glucose uptake, and increased synthesis and storage of lipid

¹Veterans Affairs Medical Center and ²Department of Medicine, University of Utah, Salt Lake City, Utah

Submitted 15 November 2004 ; accepted in final form 17 December 2004

The hexosamine signaling pathway has been shown to serve a nutrient-sensing function. We have previously shown that overexpression of the rate-limiting enzyme for hexosamine synthesis (glutamine-fructose-6-phosphate amidotransferase) in adipose tissue of transgenic mice results in skeletal muscle insulin resistance and altered regulation of leptin and adiponectin. To dissect the pathways by which the hexosamine pathway affects fuel storage and energy homeostasis, we have examined the characteristics of adipocytes from these animals. After 3 mo of age, epididymal fat pads from adult transgenic animals are 42% heavier (P = 0.003) and individual adipocytes are 23% larger in diameter (P < 0.05) than those from littermate wild-type controls. Isolated adipocytes from transgenic mice are insulin resistant, with a 2.5-fold increase in the ED₅₀ for stimulation of 2-deoxy-D-glucose uptake. However, maximal insulin-stimulated glucose uptake is increased in transgenic adipocytes by 39% (P < 0.05). This upregulation of glucose uptake was associated with a 41% increase in the expression of GLUT4 mRNA and a 28% increase in GLUT4 protein in transgenics compared with controls (P < 0.05). GLUT1 mRNA and protein did not significantly differ between fasted control and transgenics. Total lipid synthesis was also increased in epididymal adipocytes from transgenic animals by 206% compared with controls (P < 0.05). Fatty acid oxidation was increased 1.6-fold in the transgenic adipocytes (P < 0.05). We conclude that the hexosamine signaling pathway upregulates fat storage in adipocytes in states of carbohydrate excess, in part by increasing GLUT4 and glucose uptake and by augmenting fatty acid synthesis.

hexosamine; insulin resistance; adipocyte

This article has been cited by other articles:

				Y. A. Soesanto, B. Luo, D. Jones, R. Taylor, J. S. Gabrielsen, G. Parker, and D. A. McClain Regulation of Akt signaling by O-GlcNAc in euglycemia Am J Physiol Endocrinol Metab, October 1, 2008; 295(4): E974 - E980. [Abstract] [Full Text] [PDF]

				L. Tedesco, A. Valerio, C. Cervino, A. Cardile, C. Pagano, R. Vettor, R. Pasquali, M. O. Carruba, G. Marsicano, B. Lutz, et al. Cannabinoid Type 1 Receptor Blockade Promotes Mitochondrial Biogenesis Through Endothelial Nitric Oxide Synthase Expression in White Adipocytes Diabetes, August 1, 2008; 57(8): 2028 - 2036. [Abstract] [Full Text] [PDF]

				S. Marshall Role of Insulin, Adipocyte Hormones, and Nutrient-Sensing Pathways in Regulating Fuel Metabolism and Energy Homeostasis: A Nutritional Perspective of Diabetes, Obesity, and Cancer Sci. Signal., August 1, 2006; 2006(346): re7 - re7. [Abstract] [Full Text] [PDF]