EARLY INCREASED RENAL PROCOLLAGEN ALPHA-1(IV) MESSENGER-RNA LEVELS IN STREPTOZOTOCIN INDUCED DIABETES

Changes in renal procollagen mRNA levels were measured shortly after the induction of streptozotocin induced diabetes in the rat. "Medullary" procollagen alpha-1(IV) levels seven days after diabetes induction was significantly higher in untreated diabetic rats (DM, N = 12; 244 +/- 57% of the mean control value), than in diabetic rats receiving small doses of insulin insufficient to achieve euglycemia (NPH, N = 10; 87 +/- 12%) and in diluent injected nondiabetic control rats (C, N = 15; 100 +/- 12%; P < 0.01, DM vs. C and DM vs. NPH). "Medullary" procollagen alpha-1(I) mRNA levels were numerically increased in DM to a lesser degree (141 +/- 5%, ANOVA not significant) compared to C (100 +/- 13%), and this small increment was further normalized by insulin treatment (NPH, 120 +/- 11%). A trend for increased beta-actin mRNA levels in DM did not reach significance (P > 0.05). Increases in "medullary" procollagen mRNA levels did not correlate with kidney weight, glomerular tuft volume, creatinine clearance, food intake, or body weight gain, and occurred when renal morphology was normal by light microscopy. Statistically significant but weak correlations were noted between the serum glucose levels and "medullary" procollagen alpha-1(IV) mRNA levels (r = 0.43, P < 0.05). In addition, weak correlations were noted between glycosuria and "medullary" procollagen alpha-1(I) levels (r = 0.38, P < 0.05). In situ hybridization studies localized the increased procollagen alpha-1(IV) mRNA levels predominantly in the DM group primarily in the deep cortex and medullary outer stripe of proximal tubules. Glomerular procollagen alpha-1(IV), alpha-1(I), alpha-1(III) and beta-actin mRNA levels were not increased in untreated diabetic rats 7 or 28 days after diabetes induction. Thus, tubular procollagen alpha-1(IV) mRNA levels increased prior to any measurable change in glomerular levels and were ameliorated by insulin administration.