OVEREXPRESSION OF GLUT2 GENE IN RENAL PROXIMAL TUBULES OF DIABETIC ZUCKER RATS

Renal tubular reabsorption of glucose is substantially increased in hu mans and rats with diabetes mellitus, The influx of luminal glucose is mediated by Na+/glucose cotransporter system and glucose efflux from tubules to interstitium by facilitative glucose transporters (GLUT). I n Zucker diabetic rats, GLUT2 protein levels of renal proximal tubules were higher than in control litter mates: 9.67 +/- 1.95 versus 4.72 /- 1.55 (P = 0.0073). In the same proximal tubules, diabetes was assoc iated with minor decreases in GLUT1 protein levels: 1.96 +/- 0.37 for diabetics and 2.37 +/- 0.34 for controls (P = 0.12). Na+/glucose cotra nsporter system protein levels were similar in both groups, whereas Na +/K+ ATPase levels were slightly decreased in diabetic rats, but the d ifference was not statistically significant. In this report, it is sug gested that in long-term uncontrolled diabetes, GLUT2 transporters are overexpressed in renal tubules. This adaptation promotes low-affinity , high-capacity glucose efflux. The higher number of high K-m GLUT2 en sures that glucose reabsorption is increased by promoting glucose effl ux, which could be rate-limiting in the face of hyperglycemia.