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Changes in Facilitative Glucose Transporter Messenger Ribonucleic Acid Levels in the Diabetic Rat Kidney¹

Division of Endocrinology (E.C.), University of Alabama at Birmingham, and Veterans Administration Medical Center, Birmingham, Alabama; Developmental Endocrinology Branch (A.M.Z.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Diabetes Branch (Da.L., De.L.), National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; Department of Nephrology (Da.L.), Children’s Hospital National Medical Center, Washington, DC; Institute of Experimental Clinical Research (H.G.), Aarhus Kommunehospital, DK-8000 Aarhus C., Denmark

Address all correspondence and requests for reprints to: C. A. Bondy, NIH-NICHHD-DEB, Building 10/Room 10N262, 10 Center Drive, MSC-1862, Bethesda, Maryland 20892-1862.

Facilitative glucose transporter (GLUTs 1, 2, 4, and 5) messenger RNAs (mRNAs) are differentially distributed in the rat nephron: GLUT1 is widely expressed, GLUT4 is selectively concentrated in thick ascending limbs, and GLUT2 and 5 are exclusively localized in proximal tubules, consistent with differential roles for these transporters in renal glucose handling. In the present study, quantitative in situ hybridization was used to evaluate changes in these mRNA levels during acute (2 and 7 days) and chronic (30, 90, and 180 days) streptozotocin-induced diabetes mellitus (STZ-DM). Medullary GLUT1 and GLUT4 mRNA levels were significantly increased during the acute phase but returned to normal after 1 week. Cortical GLUT1 mRNA levels, however, were decreased significantly from 7 days through 6 months of STZ-DM. Cortical GLUT2 mRNA was slightly increased acutely and increased 5-fold in chronic STZ-DM, with the largest increase focally concentrated in the convoluted portion of the proximal tubule. Proximal tubule GLUT5 mRNA levels also were increased significantly during chronic STZ-DM.

In summary, medullary GLUT1 and GLUT4 mRNA levels are acutely increased in STZ-DM, paralleling the increased renal epithelial metabolic activity accompanying early diabetes. Proximal tubular GLUT2 and 5 mRNA levels were increased in chronic STZ-DM, possibly adapting to the increased need for glucose transport out of these epithelial cells, whereas the concomitant decrease in cortical GLUT1 expression may reflect the decreased requirement for basolateral import of glucose into these same cells. Thus, renal GLUTs demonstrate complex, nephron segment-specific and duration-dependent responses to the effects of STZ-DM.

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