Glucose Production in the Newborn Dog. I. Effects of Glucagon in Vivo

Abstract

Extract: Systemic glucose production rates were evaluated 4 hr after feeding in 14 newborn beagle dogs at ages between 1 and 5 days. After a prime injection of radioisotopic tracers, glucose production was determined during infusion of intermixed tracer [2-3H]glucose and [1-14C]glucose at a constant rate. Seven of the newborn dogs served as controls throughout the 3-hr period of infusion, while seven of their littermates, infused simultaneously, received glucagon at a constant rate of 3.3 μg/min between 90 and 180 min of study. In control dogs, mean glucose production, determined by dilution of [2-3H]glucose, was 55 ± 3 μmol/min · kg body weight. During the control period, their littermates produced glucose at a similar rate; however, glucagon infusion raised glucose production to 81 ± 4 μmol/min · kg.The average glucose production rate estimated with [1-14C]glucose was 88% of that with the 3H tracer during the initial control period and 77% during the glucagon infusion. In order to confirm that this discrepancy reflected the recycling of 14C and the early development of gluconeogenesis, an additional 14 newborn dogs were infused with potential substrates for [14C]glucose. In separate studies, [U-14C]lactate, [3-14C]lactate, [U-14C]alanine, and [6-14C]-glucose were incorporated into glucose and [1-14C]glucose. Quantification of gluconeogenesis by simultaneous infusion of [6-3H]glucose and [3-14C]lactate in a 5-day-old dog demonstrated that 25% of the glucose produced originated from lactate, whereas 10% was incorporated into carbon 1. Thus, systemic glucose production was established rapidly in newborn dogs and responded to stimulation with glucagon. A significant proportion of the glucose originated from recycling via the gluconeogenic pathway.Speculation: Even in well nourished newborn mammals, recycling of glucose is important in maintaining homeostasis during the postabsorptive period. Based on comparisons between dogs infused with [3-14C]lactate or [6-14C]glucose, 25% or more of hepatic glucose production may originate from glucose recycled through lactate and pyruvate. Presumably most of the rest is derived from hepatic glycogen stored in utero..