La. Wilson et al., EFFECT OF LACTATION ON INSULIN SIGNAL-TRANSDUCTION IN SHEEP ADIPOSE-TISSUE AND SKELETAL-MUSCLE, Journal of Endocrinology, 151(3), 1996, pp. 469-480
The molecular basis of the insulin resistance of adipocytes and skelet
al muscle during lactation has been investigated in sheep. The number
of insulin receptors per adipocyte or per unit membrane protein for sk
eletal muscle is unchanged by lactation. The ability of insulin to sti
mulate autophosphorylation of its beta-subunit was enhanced in adipocy
tes but not in skeletal muscle during lactation. This increased autoph
osphorylation was due, at least in part, to enhanced tyrosine phosphor
ylation and was found when both solubilised, immunoprecipitated insuli
n receptors and intact adipocytes were incubated with insulin. The abi
lity of the insulin receptor kinase to phosphorylate other proteins di
d not appear to be altered by lactation; this was shown with lectin-pu
rified insulin receptors using the artificial substrate, polyglutamyl
tyrosine, and in intact adipocytes. Lactation had no effect on the abi
lity of insulin to activate two key downstream kinases, mitogen-activa
ted protein kinase and phosphatidyl inositol-3-kinase in adipocytes. T
he study thus shows that the insulin resistance of lactation in sheep
is due to changes downstream of the receptor in both adipocytes and sk
eletal muscle.