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Metabolism of proinsulin, insulin, and C-peptide in the rat.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Katz, Adrian I. Rubenstein, Arthur H. |
| Copyright Year | 1973 |
| Abstract | The renal extraction and excretion of bovine proinsulin, insulin, and C-peptide and the contribution of the kidney to their total metabolic clearance rate (MCR) were studied in the rat. Metabolic clearance rates were measured by the constant infusion technique and plasma and urine concentrations of each polypeptide were determined by radioimmunoassay. The MCR of insulin (16.4+/-0.4 ml/min) was significantly greater than that of either proinsulin (6.7+/-0.3 ml/min) or C-peptide (4.6+/-0.2 ml/min). Metabolic clearance rates were independent of plasma levels over a range of steady-state plasma concentrations varying from 1 to 15 ng/ml.In contrast to the differences in their metabolic clearance rates, the renal disposition of the three polypeptides was similar, being characterized by high extraction and very low urinary clearance. The renal arteriovenous difference of proinsulin, insulin, and C-peptide averaged 36, 40, and 44%, respectively, and was linearly related to their arterial concentration between 2 and 25 ng/ml. When glomerular filtration was markedly reduced or stopped by ureteral obstruction, the renal extraction of proinsulin, insulin, and C-peptide was invariably greater than the simultaneously measured extraction of inulin, indicating that these polypeptides are removed from the renal circulation by both glomerular filtration and direct uptake from peritubular capillary blood. The fractional urinary clearance of each polypeptide never exceeded 0.6%, indicating that more than 99% of the amount filtered was sequestered in the kidney. The renal removal of proinsulin and C-peptide from the circulation accounts for 55 and 69% of their metabolic clerance rates, while the renal contribution to the peripheral metabolism of insulin was smaller, averaging 33%. This difference is due to the fact that insulin, but not the other two polypeptides, is metabolized to a significant extent by the liver. These results define the renal handling of proinsulin, insulin, and C-peptide in the rat and indicate that in this species the kidney represents a major site for insulin metabolism and is the main organ responsible for the degradation of proinsulin and C-peptide. |
| Starting Page | 79 |
| Ending Page | 84 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://dm5migu4zj3pb.cloudfront.net/manuscripts/107000/107277/JCI73107277.pdf |
| PubMed reference number | 4700486v1 |
| Volume Number | 52 |
| Issue Number | 5 |
| Journal | The Journal of clinical investigation |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Bos taurus C-Peptide Capillary blood Greater Than Handling (Psychology) Inulin Metabolic Clearance Rate Metabolic Process, Cellular Microgram per Liter Milliliter per Minute Ninety Nine Polypeptides Proinsulin Proinsulin, human Renal Circulation Renal Tissue Small Treatment - Filtration Ureteral obstruction glomerular filtration |
| Content Type | Text |
| Resource Type | Article |
