Assessment of Insulin Resistance in Newborn Beagles with the Euglycemic Hyperinsulinemic Clamp¹

Abstract

ABSTRACT: The developmental response to the euglycemic hyperinsulinemic clamp was assessed among newborn and adult beagles to investigate neonatal insulin resistance. Both neonatal dogs and adults were clamped at euglycemic blood glucose concentrations while receiving insulin at a rate of 3.75, 15, 30, 60, 75 or 100 mU/kg/min to generate a dose-response curve. Blood glucose levels, plasma insulin concentrations and glucose turnover rates during the basal preclamp fasting period were similar in pups and adult dogs. During the clamp period, blood glucose levels were equivalent to the preclamp period whereas plasma insulin concentrations increased. Total glucose utilization increased from 28.7 ± 18 to a plateau level of 114 ± 52.3 µmol/kg/min in adult dogs and from 30.9 ± 10.9 to 53.9 ± 28.9 /µmol/kg/min in newborn dogs. Suppression of endogenous glucose production during euglycemic hyperinsulinemia was close to 100% among adult dogs, whereas in the newborn pups, endogenous glucose production was suppressed 80%. To determine if the newborn was unable to increase glucose uptake because of a saturation effect on glucose utilization independent of insulin, another group of adult and newborn dogs received a hyperglycemic hyperinsulinemic clamp. In response to the hyperglycemic clamp, adults demonstrated an increase of glucose utilization to 261 ± 83, and newborn dogs increased utilization to 227 ± 76 µmol/kg/min. These results suggest that insulin-mediated glucose utilization in the newborn is attenuated in liver and muscle. Furthermore, these data suggest that a postreceptor defect may be present in newborn dogs when compared with the response among adults. The attenuated response is not due to a reduced capacity to utilize glucose as demonstrated by the hyperglycemic clamp. Substrate- rather than hormone-mediated events may be more important in the newborn mammal for the regulation and utilization of glucose when compared with more mature adults.

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