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. 1975 Dec;56(6):1608–1614. doi: 10.1172/JCI108243

Peripheral metabolism of insulin, proinsulin, and C-peptide in the pregnant rat.

A I Katz, M D Lindheimer, M E Mako, A H Rubenstein
PMCID: PMC333140  PMID: 1202086

Abstract

To clarify alterations in carbohydrate metabolism which occur in pregnancy, metabolic clearance rates of insulin, proinsulin, and C-peptide were measured by the constant infusion technique in term-pregnant rats and in virgin littermates. In addition, placental permeability to these peptides was evaluated by simultaneous determination of their concentration in fetal blood, amniotic fluid, and maternal arterial blood and the renal extraction and excretion of insulin and C-peptide were determined during simultaneous studies of renal hemodynamics. The metabolic clearance rate (MCR) of insulin was higher (P less than 0.005) in pregnant animals (61.5+/-1.7 ml/min per kg nonconceptus body weight) than in virgin littermates (51.5+/-2.2 ml/min per kg). Insulin disappearance from the circulation after both single injection and discontinuance of a constant infusion was also faster in gravid animals. In contrast, the MCR of proinsulin and C-peptide, and the disappearance of C-peptide from the circulation were similar in pregnant and control rats. The placenta was virtually impermeable to each of the three polypeptides since their mean levels in both fetal blood and amniotic fluid did not exceed 2.5 ng/ml and were only minimally influenced by pharmacological concentrations as high as 60 ng/ml in the maternal circulation. The renal clearance of insulin (renal arteriovenous insulin difference X renal plasma flow) was lower, and its contribution to insulin MCR was less in pregnant animals than in controls (19.4+/-1.5% vs. 28.7+/-3.7%, P less than 0.05), whereas the renal clearance and renal clearance/MCR of C-peptide were similar in pregnant rats and virgin littermates. These results indicate that the peripheral metabolism of insulin is accelerated in pregnancy, while that of pro-insulin and C-peptide is unaffected. Since transplacental passage of insulin is negligible and its renal clearance is not increased, the enhanced MCR of insulin in pregnancy is due to increased metabolism at an extrarenal site probably within the placenta itself.

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Selected References

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  1. BLEICHER S. J., O'SULLIVAN J. B., FREINKEL N. CARBOHYDRATE METABOLISM IN PREGNANCY. V. THE INTERRELATIONS OF GLUCOSE, INSULIN AND FREE FATTY ACIDS IN LATE PREGNANCY AND POST PARTUM. N Engl J Med. 1964 Oct 22;271:866–872. doi: 10.1056/NEJM196410222711702. [DOI] [PubMed] [Google Scholar]
  2. BUSE M. G., ROBERTS W. J., BUSE J. The role of the human placenta in the transfer and metabolism of insulin. J Clin Invest. 1962 Jan;41:29–41. doi: 10.1172/JCI104464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. DAVIDSON W. D., SACKNER M. A. SIMPLIFICATION OF THE ANTHRONE METHOD FOR THE DETERMINATION OF INULIN IN CLEARANCE STUDIES. J Lab Clin Med. 1963 Aug;62:351–356. [PubMed] [Google Scholar]
  4. FREINKEL N., GOODNER C. J. Carbohydrate metabolism in pregnancy. I. The metabolism of insulin by human placental tissue. J Clin Invest. 1960 Jan;39:116–131. doi: 10.1172/JCI104010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. GOODNER C. J., FREINKEL N. Carbohydrate metabolism in pregnancy. IV. Studies on the permeability of the rat placenta to I-131 insulin. Diabetes. 1961 Sep-Oct;10:383–392. doi: 10.2337/diab.10.5.383. [DOI] [PubMed] [Google Scholar]
  6. GOODNER C. J., FREINKEL N. Carbohydrate metabolism in pregnancy: the turnover of 1-131-insulin in the pregnant rat. Endocrinology. 1960 Dec;67:862–872. doi: 10.1210/endo-67-6-862. [DOI] [PubMed] [Google Scholar]
  7. Genuth S. M. Metabolic clearance of insulin in man. Diabetes. 1972 Oct;21(10):1003–1012. doi: 10.2337/diab.21.10.1003. [DOI] [PubMed] [Google Scholar]
  8. Gorden P., Hendricks C. M., Roth J. Circulating proinsulin-like component in man: increased proportion in hypoinsulinemic states. Diabetologia. 1974 Oct;10(5):469–474. doi: 10.1007/BF01221640. [DOI] [PubMed] [Google Scholar]
  9. Gorden P., Roth J. Plasma insulin: fluctuations in the "big" insulin component in man after glucose and other stimuli. J Clin Invest. 1969 Dec;48(12):2225–2234. doi: 10.1172/JCI106188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. JOSIMOVICH J. B., KNOBIL E. Placental transfer of 1-131-insulin in the rhesus monkey. Am J Physiol. 1961 Mar;200:471–476. doi: 10.1152/ajplegacy.1961.200.3.471. [DOI] [PubMed] [Google Scholar]
  11. KNOBIL E., JOSIMOVICH J. B. Placental transfer of thyrotropic hormone, thyroxine, triiodothyronine, and insulin in the rat. Ann N Y Acad Sci. 1959 Jan 9;75:895–904. doi: 10.1111/j.1749-6632.1959.tb44599.x. [DOI] [PubMed] [Google Scholar]
  12. Katz A. I., Rubenstein A. H. Metabolism of proinsulin, insulin, and C-peptide in the rat. J Clin Invest. 1973 May;52(5):1113–1121. doi: 10.1172/JCI107277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Melani F., Rubenstein A. H., Oyer P. E., Steiner D. F. Identification of proinsulin and C-peptide in human serum by a specific immunoassay. Proc Natl Acad Sci U S A. 1970 Sep;67(1):148–155. doi: 10.1073/pnas.67.1.148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mintz D. H., Chez R. A., Horger E. O., 3rd Fetal insulin and growth hormone metabolism in the subhuman primate. J Clin Invest. 1969 Jan;48(1):176–186. doi: 10.1172/JCI105966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rubenstein A. H., Pottenger L. A., Mako M., Getz G. S., Steiner D. F. The metabolism of proinsulin and insulin by the liver. J Clin Invest. 1972 Apr;51(4):912–921. doi: 10.1172/JCI106886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Smith H. W., Finkelstein N., Aliminosa L., Crawford B., Graber M. THE RENAL CLEARANCES OF SUBSTITUTED HIPPURIC ACID DERIVATIVES AND OTHER AROMATIC ACIDS IN DOG AND MAN. J Clin Invest. 1945 May;24(3):388–404. doi: 10.1172/JCI101618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Spellacy W. N., Buhi W. C., Bradley B., Holsinger K. K. Maternal, fetal and amniotic fluid levels of glucose, insulin and growth hormone. Obstet Gynecol. 1973 Mar;41(3):323–331. [PubMed] [Google Scholar]
  18. Stoll R. W., Touber J. L., Winterscheid L. C., Ensinck J. W., Williams R. H. Hypoglycemic activity and immunological half-life of porcine insulin and proinsulin in baboons and swine. Endocrinology. 1971 Mar;88(3):714–717. doi: 10.1210/endo-88-3-714. [DOI] [PubMed] [Google Scholar]
  19. TAIT J. F. REVIEW: THE USE OF ISOTOPIC STEROIDS FOR THE MEASUREMENT OF PRODUCTION RATES IN VIVO. J Clin Endocrinol Metab. 1963 Dec;23:1285–1297. doi: 10.1210/jcem-23-12-1285. [DOI] [PubMed] [Google Scholar]

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