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Relative to the human adult, persistent glucose production and greater peripheral sensitivity are characteristic of the neonatal metabolic response to insulin. To characterize the degree and duration of insulin resistance in the newborn lamb to prepare for studies of cellular mechanisms, the euglycemic hyperinsulinemic clamp technique was employed for the first time in the lamb and was combined with stable isotopic determination of glucose production[EGP] and glucose utilization[GU]. Eleven mixed breed lambs were studied at 5 days(early) or 30 days after birth (end of the neonatal period)(late). Each animal received a prime plus constant infusion of D-2 H 2 glucose in 0.45% saline at 40 μg/kg/min for 5 hrs. The basal rates of EGP and GU were determined after 3 hours. Then each animal was clamped at its own euglycemic [glucose] while receiving regular insulin at either 0 or 100 mU/kg/min for the final 2 hrs. Representative data are shown in the table. There were no significant differences in basal pl[glucose](B) or EGP(B) within the age groups, but [p < 0.0001] and [p< 0.0001] respectively between the age groups. There was a significant increase in pl [insulin](C) during the clamp in both the 100 mU/kg/min insulin groups. Neither% decline in EGP(C) during the 100 mU/kg/min insulin clamp exceeded 55%. The significant increases in the gluocse infusion rate and GU(C) were more pronounced in the younger lambs during the 100 mU/kg/min insulin clamps. In these insulin resistant lambs persistent glucose production is seen throughout the newborn period and greater peripheral sensitivity to insulin is present in the younger lambs. Compared to our prior data in the human, the lamb evidences greater insulin resistance. However, similar persistent EGP(C) and greater GU(C) in the younger lambs characterizes insulin resistance throughout the newborn period. Cellular mechanisms can be evaluated in the lamb since it metabolically parallels the human neonate in postnatal life.
Gelardi, N., Rapoza, R. & Cowett, R. Insulin Resistance, Determined with the Euglycemic Hyperinsulinemic Clamp, is Present Throughout the Newborn Period in the Lamb • 1518.
Pediatr Res43
(Suppl 4), 259 (1998). https://doi.org/10.1203/00006450-199804001-01540
