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 less than 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 greater than 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 less than 0.05). In addition, weak correlations were noted between
glycosuria and "medullary"
procollagen alpha 1(I) levels (r = 0.38, P less than 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.