The contribution of glucose to neonatal glucose homeostasis in the lamb

A multiplicity of substrates and hormones interact to influence neonatal glucose homeostasis. Based on prior studies in our laboratory, we hypothesized that glucose alone does not tightly control neonatal glucose homeostasis. Fifteen spontaneously delivered, mixed-breed term lambs, weighing 4.7 +/- 0.9 kg (mean +/- SD) were studied at 4.7 +/- 0.6 days after birth following administration of 100 mu Ci D[6,6-H-3(2)] glucose in 0.9% NaCl by the prime plus constant infusion technique to measure glucose production. After a baseline period, five lambs received 8.5 mg.kg(-1).min(-1) glucose in combination with the following to isolate the contribution of glucose: somatostatin to block insulin, glucagon, and growth hormone release; metyrapone to block cortisol release; phentolamine to block alpha-adrenergic release; and propranolol to block beta-adrenergic release (glucose + blockade). Five lambs received the above without the glucose infusion (blockade). Five lambs continued to receive 0.9% NaCl alone as the diluent for the isotopic tracer throughout the study (control). The glucose + blockade group had a significant increase in plasma glucose (P < .0001) and a significant increase in total glucose appearance (P < .0001) compared with both the blockade and control groups. Under conditions of glucose infusion at a rate 49% greater than the basal rate, the endogenous glucose production rate persisted such that there was only an evanescent decrease compared with that of the control group, which was not statistically different over time. As a substrate, glucose does not tightly control neonatal glucose homeostasis.