Possible Mechanisms and Significance of the Neonatal Surge in Glucagon Secretion: Studies in Newborn Lambs

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Abstract
Summary: Studies were conducted in newborn lambs to gain insight into the significance and mcchanism(s) responsible for the rapid rise in plasma immunoreactive glucagon (IRC) which occurs in human and other newborn species immediately after delivery. Three sets of experiments were conducted: group A, control studies (n = 5) in which delivery into room air was followed 1 hr later by cutting of the umbilical cord and periodic blood sampling for a further hour; group B, studies (n = 5) in which somatostatin (SRIF), a known inhibitor of IRG and insulin (IRI) secretion, was infused into the fetus for 10 min before, and for 1 hr after delivery and immediate cord cutting; group C, studies (n = 5) in which an identical dose regimen of SRIF was infused into fasting newborn lambs aged 24–72 hr. The doses of SRIF used were several fold higher than those proven to suppress pancreatic hormone secretion in other species. In the control studies, plasma IRG levels remained stable until the cord was cut, after which event levels rose 5–6-fold (59 ± 15 pg/ml to 305 ± 98 pg/ml, P < 0.05). Simultaneously, plasma free fatty acid (FFA) concentrations rose significantly (280 ± 80 to 780 ± 100 μEq/liter, P < 0.05) and IRI remained unchanged. Plasma glucose concentrations, however, in contrast to observations in other species, did not fall, and therefore, hypoglycemia was not the stimulus for the glucagon surge. SRIF infusion at birth (group B) did not prevent the rise in IRG. Again blood glucose values did not fall, but in contrast to the control studies plasma IRI levels rose and the rise in FFA did not occur. Later SRIF infusion (group C) resulted in a prompt and sustained suppression of IRG and IRI and a significant fall in blood glucose. These results suggest that an adrenergic mechanism rather than curtailment of nutrients is the major stimulus to the neonatal surge in IRG. Speculation: The surge in IRG following delivery is a widespread and possibly universal phenomenon in mammalian species. The surge appears to be activated by adrenergic stimuli rather than interruption of nutrient supply after separation from the placenta. In addition to the IRG rise, these adrenergic stimuli inhibit IRI secretion, thereby favoring lipolysis, glycogenolysis, and ketogenesis. These (and possibly other) hormonal changes may be key adaptive events for energy homeostasis in the transition to extrauterine life.