AJP - Renal Physiology, Vol 267, Issue 5 816-F824, Copyright © 1994 by American Physiological Society

ARTICLES

Altered renal expression of the insulin-responsive glucose transporter GLUT4 in experimental diabetes mellitus

R. G. Marcus, R. England, K. Nguyen, M. J. Charron, J. P. Briggs and F. C. Brosius 3rd
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0676.

Because the insulin-responsive glucose transporter, GLUT4, is expressed in renal vascular and glomerular cells, we determined the effects of experimental diabetes mellitus on GLUT4 expression and glucose uptake by these tissues. Quantitative reverse-transcription polymerase chain reaction studies of microdissected afferent microvessels and renal glomeruli showed that, after 1 wk of diabetes, GLUT4 mRNA was decreased to 26 and 34% of control values, respectively. GLUT4 immunoblots of renal glomerular and microvessel samples showed that GLUT4 polypeptide was decreased to 51% of control values. These results were confirmed by indirect immunofluorescence, which showed decreased GLUT4 expression in glomerular cells and in vascular smooth muscle cells of the afferent microvasculature of diabetic animals. Uptake of the glucose analogue, 2-deoxyglucose, was also depressed in microvessels of diabetic rats to 57% of control values, supporting the conclusion that fewer total glucose transporters were available for glucose uptake into diabetic renal glomerular and microvascular cells. Thus both GLUT4 expression and glucose uptake by glomerular and microvascular cells are decreased in diabetic animals. These results have led us to suggest a mechanism by which decreased renal GLUT4 expression could contribute to glomerular hyperfiltration and hypertension seen in early diabetes.

This article has been cited by other articles:

				C. L. Buller, R. D. Loberg, M.-H. Fan, Q. Zhu, J. L. Park, E. Vesely, K. Inoki, K.-L. Guan, and F. C. Brosius III A GSK-3/TSC2/mTOR pathway regulates glucose uptake and GLUT1 glucose transporter expression Am J Physiol Cell Physiol, September 1, 2008; 295(3): C836 - C843. [Abstract] [Full Text] [PDF]

				K. B. Atkins, A. Prezkop, J. L. Park, J. Saha, D. Duquaine, M. J. Charron, A. L. Olson, and F. C. Brosius 3rd Preserved expression of GLUT4 prevents enhanced agonist-induced vascular reactivity and MYPT1 phosphorylation in hypertensive mouse aorta Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H402 - H408. [Abstract] [Full Text] [PDF]

				M. Schiffer, K. Susztak, M. Ranalletta, A. C. Raff, E. P. Bottinger, and M. J. Charron Localization of the GLUT8 glucose transporter in murine kidney and regulation in vivo in nondiabetic and diabetic conditions Am J Physiol Renal Physiol, July 1, 2005; 289(1): F186 - F193. [Abstract] [Full Text] [PDF]

				G. E. Mann, D. L. Yudilevich, and L. Sobrevia Regulation of Amino Acid and Glucose Transporters in Endothelial and Smooth Muscle Cells Physiol Rev, January 1, 2003; 83(1): 183 - 252. [Abstract] [Full Text] [PDF]

				D. Feliers, M. A. Frank, and D. J. Riley Activation of Cyclin D1-Cdk4 and Cdk4-Directed Phosphorylation of RB Protein in Diabetic Mesangial Hypertrophy Diabetes, November 1, 2002; 51(11): 3290 - 3299. [Abstract] [Full Text] [PDF]

				H. IKENAGA, J. P. BAST, R. W. FALLET, and P. K. CARMINES Exaggerated Impact of ATP-Sensitive K+ Channels on Afferent Arteriolar Diameter in Diabetes Mellitus J. Am. Soc. Nephrol., July 1, 2000; 11(7): 1199 - 1207. [Abstract] [Full Text]

				H. Shen, D. E. Smith, T. Yang, Y. G. Huang, J. B. Schnermann, and F. C. Brosius III Localization of PEPT1 and PEPT2 proton-coupled oligopeptide transporter mRNA and protein in rat kidney Am J Physiol Renal Physiol, May 1, 1999; 276(5): F658 - F665. [Abstract] [Full Text] [PDF]

				T. J. Anderson, S. Martin, J. L. Berka, D. E. James, J. W. Slot, and J. L. Stow Distinct localization of renin and GLUT-4 in juxtaglomerular cells of mouse kidney Am J Physiol Renal Physiol, January 1, 1998; 274(1): F26 - F33. [Abstract] [Full Text] [PDF]