Insulin-Dependent Glucose Utilization in Intensively Milk-Fed Veal Calves Is Modulated by Supplemental Lactose in an Age-Dependent Manner

摘要

Postprandial insulin resistance with excessive hyperinsulinemia, hyperglycemia and glucosuria develops with increasing age in veal calves intensively fed milk replacers. We tested the age dependency of insulin resistance, modulated by high lactose intake, glucose oxidation and insulin receptor number and affinity after an overnight period without food. Male calves were fed a milk replacer containing 290 or 423 g lactose and 310 and 541 g total sugar/kg from 69–195 kg body weight. At mean body weights of 95 and 170 kg, insulin-dependent glucose metabolism was studied in euglycemic-hyperinsulinemic glucose clamps (EGC), and glucose-dependent insulin responses were tested in hyperglycemic clamps (HGC). EGC were combined with infusions of [13C6]glucose to measure glucose kinetics and glucose oxidation by determination of 13CO2 exhalation. During EGC and HGC, insulin concentrations were similar in both groups, indicating comparable insulin secretion and metabolic clearance rates. On the basis of glucose infusion rates required to maintain eu- or hyperglycemia in EGC and HGC, respectively, insulin-dependent glucose utilization was not age dependent. However, in calves receiving a high lactose intake, insulin-dependent glucose utilization was enhanced in the early phases, but was reduced in the late stages of the growth trial. Insulin-dependent glucose utilization behaved inversely with atom % excess of [13C6]glucose, but changed in a manner similar to that of the rate of glucose appearance. Inhibition of endogenous glucose output, exhalation of 13CO2 and amounts of oxidized glucose exhibited no group differences. More glucose was therefore stored in lactose-supplemented calves. A reduced insulin receptor number in skeletal muscle in calves fed high amounts of lactose likely contributed to low insulin-dependent glucose utilization.