Ligand-induced translocation of insulin receptors in intact rat liver.

The effects of a single injection of insulin (25 nmol/ 100 g of body weight) on the subcellular distribution of insulin and the insulin receptors in liver were examined in rats.Injected insulin rapidly associates with the total particulate fraction; it is concentrated first in plasma membranes (1 pmol/mg of protein at 15 s) and later in the light, intermediate, and heavy Golgi fractions (3, 15, and 8 pmol/mg, respectively, at 8 min).Insulin treatment causes a delayed (8 min) 2-fold decrease in the insulin binding activity of the total particulate fraction; this change does not occur with Triton X-100extracted particles.The Triton-extractable insulin binding activity decreases by 50% in plasma membranes and 30% in the residual (Golgi-free) microsomal fraction; concomitantly, it increases by 4-to 5-fold in Golgi fractions.These changes occur in 90 s, achieve maximum from 8 to 40 min, and undergo full reversal from 40 min to 3 h.At 3 h, binding activity in Golgi fractions is reduced by 2-to 3-fold.The doses of insulin producing half-maximal effects in plasma membranes and in Golgi fractions (intermediate and heavy) are, respectively, 1 and 0.03 nmol/100 g.The altered insulin binding activity in all fractions results solely from a change in receptor number.Insulin treatment causes an early 25% increase and a delayed 60% decrease in protein yield in the light and intermediate Golgi fractions.The binding sites lost from plasma membranes and the residual microsomal fraction (11% of the total) are nearly quantitatively recovered in Golgi fractions (9.5%).Insulin treatment causes little changes in the subcellular distribution of plasma membrane and Golgi marker enzymes, glucagon receptors, and wheat germ agglutinin-binding sites.It is suggested that acute occupancy of insulin receptors in hepatocytes leads to their rapid, specific, and reversible translocation within the cell without affecting their total number.10852