Regulation of insulin receptor functions by a peptide derived from a major histocompatibility complex class I antigen.
A 25 residue peptide, Dk-(61-85), derived from the alpha 1 domain of a murine MHC class I molecule (H-2Dk), enhances cellular glucose uptake, prolongs the effect of insulin, and inhibits insulin receptor internalization without affecting insulin binding or dissociation. Full effect of the peptide is obtained at 10-100 microM. The magnitude of the peptide-mediated enhancement of glucose uptake is insulin dependent and is at maximum approximately 50% above that of full insulin stimulation, excluding a merely insulinomimetic action of the peptide. Dk-(61-85) does not interact directly with the glucose transporter molecule. Furthermore, the peptide-mediated inhibition of insulin receptor internalization results in 2-3 times more receptors in the plasma membrane. The peptide also causes hypoglycemia in rats. The biological activity of Dk-(61-85) suggests that an important nonimmunological role of MHC class I molecules is to affect some of the key functions of ligand-activated receptors.
Stagsted
J
J
Receptron, Inc., Concord, California 94520.
Reaven
G M
GM
Hansen
T
T
Goldstein
A
A
Olsson
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004705:Endocytosis; D005947:Glucose / Q000378:metabolism; D006183:H-2 Antigens / Q000502:physiology*; D007328:Insulin / Q000502:physiology; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000502:physiology*; D013329:Structure-Activity Relationship
D001786:Blood Glucose; D006183:H-2 Antigens; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D010446:Peptide Fragments; D011972:Receptor, Insulin; D005947:Glucose