INCREASED INVIVO INSULIN SENSITIVITY BUT NORMAL LIVER INSULIN-RECEPTOR KINASE-ACTIVITY IN DWARF CHICKENS

The effects of the recessive and sex-linked dw gene on insulin sensitivity and liver insulin receptors were compared in normal (Dw-dw) and dwarf (dw-dw) brother or half-brother chickens. At 3.5 weeks of age, following an overnight fast, exogenous insulin (0-6.9 nmol/kg body weight) was slightly but significantly more hypoglycaemic in dwarf chickens. At 4 weeks of age, following an oral glucose load (2 g/kg), glucose tolerance was the same in both genotypes, whereas plasma insulin levels were greatly decreased in dwarf chickens. At 5 weeks of age, plasma concentrations of glucose and insulin were the same in both genotypes in the fasting state and decreased in the fed state in dwarf chickens. In liver membranes prepared from fasted chickens, insulin binding was increased in dwarf chickens, while the affinity of insulin receptors and the insulin-degrading activity of the membranes were the same in both genotypes. Following solubilization with Triton X-100, liver receptors were successively purified on lentil then wheat germ lectins. Autophosphorylation of the β-subunit did not differ between either the genotype or the nutritional (fed or fasted) state. In the basal state (in the absence of insulin) the tyrosine kinase activity of the receptor towards artificial substrate poly(Glu,Tyr)4:1 was significantly decreased in dwarf chickens by fasting. However, the change in tyrosine kinase activity of the receptor in response to insulin was similar, irrespective of the genotype and the nutritional state. Therefore, the slight increase in insulin sensitivity observed in vivo in dwarf chickens is accounted for, at least partly, by a slight increase in liver insulin receptor number, but not by a change in the kinase activity of liver insulin receptors. In addition, post-insulin receptor kinase events and/or GH-dependent counter-regulatory mechanisms may superimpose and increase the insulin sensitivity of dwarf chickens.