Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

In vivo insulin resistance during pregnancy in the rat

  • 140 Accesses

  • 37 Citations


The glucose disappearance rate measured after IV glucose injection (1 g/kg body wt) remained unchanged between 12 and 21 day of gestation in the rat. In contrast, insulin secretion in response to IV glucose was markedly increased on day 19 and 21 of pregnancy, suggesting resistance to endogenous insulin. Glucose kinetics (glucose production, utilization and clearance) in response to various doses of IV insulin have been studied in anaesthetised postabsorbtive 19 day pregnant and virgin rats using 6-3H glucose. With the supramaximal dose of insulin (4 U/kg body wt) no differences in glucose kinetics were found between pregnant and virgin rats. In contrast, with the two lower doses of insulin (0.15 and 0.05 U/kg body wt) glucose production was inhibited by 36±3% and 13±2% (Mean±SEM) respectively in virgin rats, but was not decreased in pregnant rats. When the effect of insulin on glucose clearance was expressed as % of the maximal effect obtained with 4 U/kg body weight, the rise in glucose clearance in response to the two lower doses of insulin (0.15 and 0.05 U/kg body wt) was lower in pregnant (57.5±6 and 27.4±4%) than in virgin rats (73.3±6 and 42.2±7%). These results suggest that a decreased sensitivity to insulin appears in late pregnancy in the rat and could involve both liver and skeletal muscle.


  1. 1.

    Pedersen J (1977) The pregnant diabetic and her newborn. Munksgaard, Copenhagen, p 22–30

  2. 2.

    Kalkhoff RK, Kissebah AH, Kim HJ (1978) Carbohydrate and lipid metabolism during normal pregnancy: relationship to gestational hormone action. Semin Perinatol 2: 291–308

  3. 3.

    Fisher PM, Sutherland HW, Bewsher PD (1979) Insulin response studies in normal pregnancy and chemical gestational diabetes. In: Sutherland HW, Stowers JM (ed) Carbohydrate metabolism in pregnancy and the newborn, 1978. Springer, Berlin Heidelberg New York p 47–61

  4. 4.

    Burt RL (1956) Peripheral utilization of glucose in pregnancy III) Insulin tolerance. Obstet Gynecol 2: 658–664

  5. 5.

    Yen SSC (1973) Endocrine regulation of metabolic homeostasis during pregnancy. Clin Obstet Gynecol 16: 130–147

  6. 6.

    Costrini NV, Kalkhoff RK (1971) Relative effects of pregnancy, estradiol and progesterone on plasma insulin and pancreatic islet insulin secretion. J Clin Invest 50: 992–999

  7. 7.

    Knopp RH, Ruder HJ, Herrera E, Freinkel N (1970) Carbohydrate metabolism in pregnancy VII) Insulin tolerance during late pregnancy in the fed and fasted rat. Acta Endocrinol (Kbh) 65: 352–360

  8. 8.

    Girard JR, Cuendet GS, Marliss EB, Kervran A, Rieutort M, Assan R (1973) Fuels, hormones and liver metabolism at term and during the early postnatal period in the rat. J Clin Invest 52: 3190–3200

  9. 9.

    Katz AI, Lindheimer MD, Mako ME, Rubenstein AH (1975) Peripheral metabolism of insulin, proinsulin and C-peptide in the pregnant rat. J Clin Invest 56: 1608–1614

  10. 10.

    Steele R (1959) Influences of glucose loading and of injected insulin on hepatic glucose output. Ann NY Acad Sci 82: 420–430

  11. 11.

    Sacca L, Perez G, Carteni G, Rengo F (1977) Evaluation of the role of the sympathetic nervous system in the glucoregulatory response to insulin-induced hypoglycemia in the rat. Endocrinology 101: 1016–1022

  12. 12.

    Radziuck J, Norwich KH, Vranic M (1978) Experimental validation of measurements of glucose turnover in nonsteady state. Am J Physiol 234: E84-E93

  13. 13.

    Cherrington AD, Williams PE, Harris MS (1978) Relationship between the plasma glucose level and glucose uptake in the conscious dog. Metabolism 27: 787–791

  14. 14.

    Wilcoxon F (1947) Probability tables for individual comparisons by ranking methods. Biometrics 3: 119–122

  15. 15.

    Shah JH, Wongsurawat N, Aran PP, Motto GS, Bowser EN (1977) A method for studying acute insulin secretion and glucose tolerance in unanesthetized and unrestrained rats. The effects of mild stress on carbohydrate metabolism. Diabetes 26: 1–6

  16. 16.

    Young JB, Landsberg L (1979) Sympathoadrenal activity in fasting pregnant rats. Dissociation of adrenal medullary and sympathetic nervous system responses. J Clin Invest 64: 109–116

  17. 17.

    Herrera E, Knopp RH, Freinkel N (1969) Urinary excretion of epinephrine and norepinephrine during fasting in late pregnancy in the rat. Endocrinology 84: 447–450

  18. 18.

    Kahn CR (1978) Insulin resistance, insulin insensitivity and insulin unresponsiveness: a necessary distinction. Metabolism 27 [Suppl 2]: 1893–1902

  19. 19.

    Owen OE, Felig P, Morgan AP, Wahren J, Cahill GF Jr (1969) Liver and kidney metabolism during prolonged starvation. J Clin Invest 48: 574–583

  20. 20.

    Domont LA, Freinkel N, Baumann G (1978) Insulin receptors in liver are decreased in pregnancy. Clin Res 26: 479A

  21. 21.

    Soman V (1979) Heterogeneity of insulin receptor changes in pregnancy. Diabetes 28: 393

  22. 22.

    Flint DJ (1980) Change in the number of insulin receptors of isolated rat hepatocytes during pregnancy and lactation. Biochim Biophys Acta 628: 322–327

  23. 23.

    Bergman EN (1963) Quantitative aspects of glucose metabolism in pregnant and nonpregnant sheep. Am J Physiol 204: 147–152

  24. 24.

    Kalhan SC, D'Angelo LJ, Savin SM, Adam PAJ (1979) Glucose production in pregnant women at term gestation. Sources of glucose for human fetus. J Clin Invest 63: 388–394

  25. 25.

    Boyd RDH, Morriss FH, Meschia G, Makowski EL, Battaglia FC (1973) Growth of glucose and oxygen uptakes by fetuses of fed and starved ewes. Am J Physiol 225: 897–902

  26. 26.

    Beaton GH, Beare J, Ryu MH, McHenry EW (1954) Protein metabolism in pregnant rat. J Nutr 54: 291–304

  27. 27.

    Knopp RH (1978) Fuel metabolism in pregnancy. Contemp Obstet Gynecol 1: 83–90

  28. 28.

    Curtis-Prior PB, Trethewey J, Stewart GW, Hanley T (1969) The contribution of different organs and tissues of the rat to assimilation of glucose. Diabetologia 5: 384–391

  29. 29.

    Rushakoff R, Kalkhoff RK (1979) Effects of pregnancy and sex steriods on skeletal muscle sensitivity to insulin. Clin Res 27: 703

  30. 30.

    Leake NH, Burt RL (1966) Response of rat adipose tissue to insulin during pregnancy. Am J Obstet Gynecol 96: 131–133

  31. 31.

    Knopp RH, Herrera E, Freinkel N (1970) Carbohydrate metabolism in pregnancy. VIII) Metabolism of adipose tissue isolated from fed and fasted pregnant rats during late gestation. J Clin Invest 49: 1438–1446

  32. 32.

    Flint DJ, Sinnett-Smith PA, Clegg RA, Vernon RG (1979) Role of insulin receptors in the changing metabolism of adipose tissue during pregnancy and lactation in the rat. Biochem J 182: 421–427

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Leturque, A., Ferré, P., Satabin, P. et al. In vivo insulin resistance during pregnancy in the rat. Diabetologia 19, 521–528 (1980).

Download citation

Key words

  • Pregnant rat
  • insulin resistance
  • glucose tolerance
  • glucose production
  • glucose utilization
  • glucose turnover
  • insulin sensitivity