Insulin antagonism: a novel role for human serum transferrin.
We have purified alpha2-glycoprotein (alpha2-GP), an insulin antagonist from human plasma which is induced by growth hormone (GH), and shown that pure alpha2-GP is a potent antagonist of severe insulin-induced hypoglycemia, producing acute hyperglycemia in intact rats and ketonuria in diabetic rats. The N-terminal amino acid sequence of alpha2-GP and the reactivity of alpha2-GP with an antitransferrin monoclonal antibody show that alpha2-GP is identical to human serum transferrin. Furthermore, pure human serum transferrin and non-glycosylated recombinant human transferrin reproduce the insulin antagonist effects of alpha2-GP in rats, whereas ovotransferrin shows no such effect. The neutralization of the insulin antagonism of human serum transferrin by an anti-transferrin monoclonal antibody shows that transferrin has a new function as a potent insulin antagonist. This novel role for human serum transferrin in the regulation of glucose metabolism provides a reasonable mechanism for the diabetogenic effect of GH, and has important implications for the etiology and progression of diabetes.
Vargas
L
L
Department of Cell and Molecular Biology, Pontifical Catholic University of Chile, Santiago.
Kawada
M E
ME
Bazaes
S
S
Karplus
P A
PA
Faerman
C H
CH
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D006023:Glycoproteins / Q000097:blood / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007329:Insulin Antagonists / Q000097:blood*; D007700:Kinetics; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017385:Sequence Homology; D014168:Transferrin / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D006023:Glycoproteins; D007328:Insulin; D007329:Insulin Antagonists; D010446:Peptide Fragments; D014168:Transferrin