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Pregnancy and Undernutrition Alter Glucose Metabolic Responses to Insulin in Sheep^{1, 2, 3,}

Department of Animal Science, Cornell University, Ithaca, NY 14853-4801

Nonpregnant and late-pregnant ditocous ewes were fed either to maintain zero energy balance in maternal tissues (fed) or at 50% of this level (underfed) for several weeks. Whole-body kinetics of glucose metabolism were measured under basal conditions, and the hyperinsulinemic, euglycemic clamp technique was used to define insulin-dose response profiles for several indices of whole-body glucose utilization, and for endogenous glucose production. Pregnancy increased and undernutrition decreased basal glucose entry rate (GER), glucose metabolic clearance rate (GMCR) and insulin-independent glucose utilization (IIGU). The consistent increment in IIGU of pregnant over nonpregnant ewes was comparable to previous estimates of uterine glucose uptake. Pregnancy resulted in higher plasma concentration for 50% maximal responses (ED₅₀) to insulin of GER, GMCR, steady-state glucose infusion rate (SSGIR) to maintain euglycemia and insulin-dependent glucose utilization (IDGU). These changes were especially large in underfed pregnant ewes. Effects on the maximal response to insulin of these variables (R_max) were relatively small (GMCR, IDGU) or nonsignificant (GER, SSGIR). Maximum insulin-induced suppression of endogenous glucose production was significantly lower due to undernutrition; neither R_max nor ED₅₀ for this response was affected by pregnancy. Insulin resistance in late-pregnant ewes is primarily due to decreased insulin sensitivity in (presumably) peripheral tissues, implying an alteration of receptor function or of early postreceptor signal transduction.

KEY WORDS: • undernutrition • glucose metabolism • pregnancy • insulin • sheep

¹ Presented in part at the 83rd Annual Meeting of the American Society of Animal Science, August 1991, Laramie, WY [Petterson, J. A., Dunshea, F. R. & Bell, A. W. (1991) Insulin resistance in pregnant and underfed sheep. J. Anim. Sci. 69(suppl. 1): 314 (abs.)].

² Supported by Cornell University Agricultural Experiment Station.

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ Current address: Victorian Institute of Animal Science, Department of Agriculture, Werribee VIC 3030, Australia.

⁵ To whom correspondence and reprint requests should be addressed.

Manuscript received 30 December 1992. Revision accepted 19 March 1993.

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