This Article Full Text Full Text (PDF) 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 Collier, J. J. Articles by Scott, D. K. Search for Related Content PubMed PubMed Citation Articles by Collier, J. J. Articles by Scott, D. K.

Sweet Changes: Glucose Homeostasis Can Be Altered by Manipulating Genes Controlling Hepatic Glucose Metabolism

Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112

Address all correspondence and requests for reprints to: Donald K. Scott, Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, Louisiana 70112. E-mail: dscott3{at}lsuhsc.edu.

The liver is responsible for glucose synthesis in the fasting state, and glucose uptake, storage, and utilization in the fed state. A phenotypic switch, normally initiated by insulin or glucagon, controls the transition between the two states, which includes transcriptional alterations that regulate metabolic enzyme abundance for multiple metabolic pathways in a coordinated manner. A network of transcription factors, coactivators, and corepressors direct these changes, thus acting as transcriptional sensors of the nutritional status of an organism. The inability of the hepatocyte to undergo this metabolic reprogramming is characteristic of diabetes mellitus. Modulations that control the amount of individual metabolic enzymes or transcription factors can initiate the fasting-to-fed transition of the hepatocyte in an insulin-independent manner. Alternatively, overexpression of key regulators of metabolism can lock hepatocytes in the fasted state. These manipulations alter hepatic glucose flux, leading to either amelioration or induction of diabetes mellitus. These maneuvers reveal the complexity of the coordinated mechanisms used by the liver to alter its phenotype and provide evidence for the control strength of metabolic signaling.

This article has been cited by other articles:

				T. P. Torres, R. L. Catlin, R. Chan, Y. Fujimoto, N. Sasaki, R. L. Printz, C. B. Newgard, and M. Shiota Restoration of Hepatic Glucokinase Expression Corrects Hepatic Glucose Flux and Normalizes Plasma Glucose in Zucker Diabetic Fatty Rats Diabetes, January 1, 2009; 58(1): 78 - 86. [Abstract] [Full Text] [PDF]

				C. Wu, S. A. Khan, L.-J. Peng, H. Li, S. G. Carmella, and A. J. Lange Perturbation of glucose flux in the liver by decreasing F26P2 levels causes hepatic insulin resistance and hyperglycemia Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E536 - E543. [Abstract] [Full Text] [PDF]

				E. M Scott, A. M Carter, and J. B. Findlay The application of proteomics to diabetes Diabetes and Vascular Disease Research, May 1, 2005; 2(2): 54 - 60. [Abstract] [PDF]