CHANGES IN FACILITATIVE GLUCOSE-TRANSPORTER MESSENGER-RIBONUCLEIC-ACID LEVELS IN THE DIABETIC RAT-KIDNEY

Facilitative glucose transporter (GLUTs 1, 2, 4, and 5) messenger RNAs (mRNAs) are differentially distributed in the rat nephron: GLUT1 is w idely 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 glu cose handling. In the present study, quantitative in situ hybridizatio n was used to evaluate changes in these mRNA levels during acute (2 an d 7 days) and chronic (30, 90, and 180 days) streptozotocin-induced di abetes mellitus (STZ-DM). Medullary GLUT1 and GLUT4 mRNA levels were s ignificantly increased during the acute phase but returned to normal a fter 1 week. Cortical GLUT1 mRNA levels, however, were decreased signi ficantly from 7 days through 6 months of STZ-DM. Cortical GLUT2 mRNA w as slightly increased acutely and increased 5-fold in chronic STZ-DM, with the largest increase focally concentrated in the convoluted porti on 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, paralleli ng the increased renal epithelial metabolic activity accompanying earl y diabetes. Proximal tubular GLUT2 and 5 mRNA levels were increased in chronic STZ-DM, possibly adapting to the increased need for glucose t ransport out of these epithelial cells, whereas the concomitant decrea se in cortical GLUT1 expression may reflect the decreased requirement for basolateral import of glucose into these same cells. Thus, renal G LUTs demonstrate complex, nephron segment-specific and duration-depend ent responses to the effects of STZ-DM.