Insulin antagonism: a novel role for human serum transferrin

• Published in: Hormone and metabolic research Vol. 30; no. 3; p. 113
• Main Authors: Vargas, L, Kawada, M E, Bazaes, S, Karplus, P A, Faerman, C H
• Format: Journal Article
• Language: English
• Published: Germany 01-03-1998
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - pharmacology; Blood Glucose - metabolism; Glycoproteins - blood; Glycoproteins - pharmacology; Humans; Insulin - pharmacology; Insulin Antagonists - blood; Kinetics; Male; Mice; Peptide Fragments - chemistry; Rats; Rats, Sprague-Dawley; Sequence Homology; Transferrin - chemistry; Transferrin - pharmacology; Transferrin - physiology
• ISSN: 0018-5043
• DOI: 10.1055/s-2007-978847

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.