Effects of Euglycemic Hyperinsulinemia on Neonatal Canine Hepatic and Muscle Metabolism

Abstract

ABSTRACT. The effects of euglycemic hyperinsulinemia on hepatic and muscle metabolism were determined in the fasted newborn dog during the first day of life. Hyperinsulinemia was sustained with a primed constant infusion of insulin whereas euglycemia was maintained with an intravenous infusion of 10% glucose using the insulin clamp technique. Euglycemic hyperinsulinemia caused an increase of glucose utilization from 43.9 f 3.7 to 66.5 + 5.4 ~mol/kg/min ( p < 0.001) and reduced endogenous glucose production to 44.4 f 5.4% of basal values obtained before the induction of hyperinsulinemia. Hepatic tissue glycogen, triglycerides, or intermediates were not altered by hyperinsulinemia nor was the incorporation of [3Hjglucose into glycogen. However, the hepatic cytoplasmic redox state was more oxidized, and the incorporation of [3Hjglucose into triglycerides was higher among hyperinsulinemic pups. Pups who demonstrated incomplete suppression of endogenous glucose production had metabolite perturbation suggestive of ongoing gluconeogenesis. Despite very few changes in hepatic tissue metabolite levels, pups subjected to hyperinsulinemia demonstrated a linear uptake of 2-

Very Immature Infants (≤ 30 Wk) Respond to Glucose Infusion with Incomplete Suppression of Glucose Production

“…Clamp experiments have shown incomplete suppression of glucose production in puppies despite very high insulin levels, whereas total suppression was found in adult dogs at corresponding insulin levels (6,7). These results indicate the presence of insulin resistance in the puppies (6,7). Corresponding observations were made by Cowett et al (8) in comparisons of lambs and ewes.…”

“…It has been discussed whether the defective glucose regulation in newborn infants and animals is due to lack of a hepatic response to an increased plasma glucose concentration, low insulin secretion, or hepatic or peripheral insulin resistance. Clamp experiments have shown incomplete suppression of glucose production in puppies despite very high insulin levels, whereas total suppression was found in adult dogs at corresponding insulin levels (6,7). These results indicate the presence of insulin resistance in the puppies (6,7).…”

“…In contrast to the situation in newborns, glucose infusion has been found to cause a complete suppression of glucose production in both adult humans and adult animals (5)(6)(7)(8). It has been discussed whether the defective glucose regulation in newborn infants and animals is due to lack of a hepatic response to an increased plasma glucose concentration, low insulin secretion, or hepatic or peripheral insulin resistance.…”

“…infusions of glucose at a low rate, hyperglycemia is a commonly observed complication in very immature infants, indicating defective glucose regulation (3,4). In adults and experimental animals, the glucose production is completely suppressed when glucose is given at a rate corresponding to the basal hepatic output (5)(6)(7)(8). The adult concentration increased from 6 a 2 to 11 ?…”

Insulin Receptor Number and Binding Affinity in Newborn Dogs

“…Insulin resistance has been previously investigated in our laboratory using the euglycemic hyperinsulinemic clamp technique in newborn and adult dogs. Newborn dogs did not consistently suppress endogenous glucose production and never achieved maximal glucose metabolization in the presence of hyperinsulinemia when compared with adult dogs (9). These studies indicated that insulin resistance in the newborn dog occurred in the liver (continued glucose production) and skeletal muscle (reduced glucose metabolization).…”