Endogenous Glucose Production during Constant Glucose Infusion in the Newborn Lamb

Abstract

Summary: Prompt diminution of endogenous hepatic glucose production is characteristic of the mature (adult) response to exogenous glucose infusion. We have tested the validity of this hypothesis in the neonatal period in 26 unanesthetized mixed breed term lambs and for comparison in eight 4− to 5-month-old mixed breed sheep. After a 7-hr fast, basal plasma glucose, insulin, and glucagon concentrations were determined following which the term lambs received either no glucose or 5.7, 11.7, or 21.7 mg glucose/kg/min over a period of 6 hr, and the 5-month-old sheep received either none or 5.7 mg glucose/kg/min. Glucose turnover was determined by the prime-constant infusion technique of Steele using ³H₆ radiolabeled glucose during a 50-min turnover period which followed the 6-hr infusion of 0.45% saline or varying doses of glucose following the onset of fasting by 14 hr. Both newborn and adult animals maintained a constant plasma glucose concentration and glucose specific activity during the turnover period. Endogenous glucose production persisted in the term lamb until the exogenous glucose infusion reached the rate of 21.7 mg/kg/min. In contrast, the adult lambs reduced their endogenous glucose production with an exogenous glucose infusion rate of 5.7 mg/kg/min. At the time the endogenous glucose production rates were significantly reduced, the plasma insulin level in the newborn lamb was 5-fold greater than that of the adult sheep.

Under steady state conditions of plasma glucose concentration and glucose specific activity, our data suggest that there is imprecise control of endogenous glucose production in the newborn lamb in contrast to the older sheep of 4–5 months of age. The absence of precise control may be due to decreased hepatic sensitivity for insulin.

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