The Handling of Insulin, Proinsulin, and C-peptide by the Isolated Rat Kidney

The renal handling of proinuslin, insulin, and C-peptide was studied in the isolated perfused rat kidney. At perfusate peptide concentrations below 12 ng./ml. (control value), the organ clearance of proinsulin (637 ± 74 μl. per minute) was significantly (P < 0.001) lower than that of insulin (1,276 ± 48 μl. per minute) and C-peptide (1,618 ± 218 μl. per minute). There was a significant (P < 0.001) inverse correlation between the organ clearance and the molecular size of the peptide (r = − 0.86). As the glomerular filtration rate was 53 per cent of the organ clearance of proinsulin, 16 per cent of the organ clearance of insulin, and 27 per cent of the organ clearance of C-peptide, it was evident that a mechanism for extracting these peptides from the peritubular circulation exists. When kidneys were perfused with insulin in concentrations above 330 ng./ml., the organ clearance fell to approximately half the control value and its fractional urinary excretion increased several fold, indicating saturation of luminal absorption of filtered insulin. As the fall in organ clearance of insulin was larger than any decrease in the rate of insulin filtration that may have occurred, we conclude that at high insulin concentrations saturation of contraluminal uptake of insulin also occurs. Similarly, the organ clearance of C-peptide declined to 46 per cent of the control level at perfusate concentrations of 108 to 301 ng./ml. In contrast, despite perfusing kidneys with concentrations of proinsulin as high as 367 ng./ml., its organ clearance and fractional urinary excretion did not decline. There was no evidence of conversion of proinsulin to insulin or C-peptide.