Reduced insulin binding to hepatic plasma membranes in D-galactosamine-treated rats.
Six to 12 hr after IP injection of 400 mg/kg of D-galactosamine in rats a 5-fold increase in plasma insulin was observed. In addition, impaired glucose assimilation was present after an IV Load in spite of unchanged fasting glucose levels. In streptozotocin-diabetic rats (100 mg/kg IV) plasma insulin remained diminished 12 h after induction of D-galactosamine hepatitis. Under identical conditions of preparation and incubation, the liver plasma membranes of D-galactosamine-treated rats, in both normal and diabetic states, bound only 40--60% as much insulin per mg of membrane protein as those of the control rats. Scatchard analysis suggested that this was due to a decrease in the number of receptor sites in the membranes of the D-galactosamine-injected rats. No difference in the insulin degrading capacity and in insulin-receptor dissociation of the plasma membranes between control and D-galactosamine-treated groups was found. These data suggest that a reduction in the number of hepatic insulin receptors in galactosamine hepatitis can lead to insulin resistance and hyperinsulinaemia.
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005688:Galactosamine / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D011972:Receptor, Insulin