Blunted muscle responsiveness to insulin in the neonatal rat

Peripheral muscle responsiveness to insulin was studied in neonatal rats in vivo by measuring net incorporation of radiolabeled glucose to glycogen in diaphragm. D(U-¹⁴C) glucose, 0.03 μCi/g rat pup weight, was injected i.p. with or without (control) insulin 5000 μU/g rat pup weight into pups from 86 litters of Sprague-Dawley rats as well as into 16 adult rats by the technique of Rafaelson. Diaphragms were excised after a 30-min in vivo exposure at birth, 24, 48, 72, or 168 hr of age and in the adult rats. Insulin increased net incorporation of radiolabeled glucose into diaphragm glycogen in comparison to age-matched controls (p < 0.025). The percent stimulation by insulin of labeled glucose into diaphragm glycogen was low at birth (250%) and at 24 hr (200%), but increased with advancing age and approached adult levels by 168 hr (1270%). At birth and at 24 hr, a 5-log insulin dose-response curve showed significant net incorporation only at 5000 μU insulin/g rat pup weight; by 72 hr a significant increase was noted at 50 μU insulin/g rat pup weight. Muscle glycogen concentration was high at birth ($\text{1.22 mg}\text{100 mg tissue}$), fell to 50% of the birth value from 24 through 168 hr, and could not account for the decreased insulin response noted. Decreased uptake of deoxyglucose into diaphragm in vivo paralleled the reduced net incorporation of radiolabeled glucose into diaphragm glycogen during the time period studied. The data are interpreted to indicate a blunted responsiveness of skeletal muscle to insulin during the first 48 hr in rats, which is related to decreased sensitivity of hexose transport to insulin.