title: The potentiations by insulin-stimulating peptide from bovine serum albumin of the effects of insulin mimickers and insulin in stimulating glucose utilization by rat adipocytes.
abstract: An insulin-stimulating peptide derived from bovine serum albumin by digestion with trypsin was shown to inhibit insulin degradation. Addition of this peptide (1.2 microM) to the medium of isolated rat adipocytes markedly inhibited the degradation of insulin in the medium, but had a little effect on degradation of cell-associated insulin. Moreover, this peptide did not prevent dissociation of cell-associated insulin, suggesting that it is a bacitracin-type, not a chloroquine-type inhibitor of insulin degradation. The peptide also potentiated the stimulation by insulin mimickers of glucose oxidation by rat adipocytes, strongly indicating that it has some other effects besides inhibition of insulin degradation. Therefore, the effect of the peptide on activation of pyruvate dehydrogenase (PDH), one of the postbinding actions of insulin, was studied. Addition of the peptide (4 microM) to adipocytes was found to activate PDH in the absence or presence of insulin. This stimulatory effect of the peptide on PDH was dose-dependent and was observed in both whole cells and subcellular fractions of rat adipocytes. The peptide also stimulated PDH in a subcellular system of either plasma membranes and mitochondria or mitochondria only. Sodium fluoride, an inhibitor of phosphatase, blocked the action of the peptide almost completely, suggesting that the stimulatory effect of the peptide on PDH activity is at least partly due to its activation of PDH phosphatase. The mechanisms of action of the peptide are discussed. The peptide should be useful in studies on modulation of the action of insulin.
authors.affiliation: Department of Biochemistry, School of Dentistry, University of Tokushima.
authors.forename: A
authors.initials: A
authors.lastname: Ueno
authors.forename: N
authors.initials: N
authors.lastname: Arakaki
authors.forename: S
authors.initials: S
authors.lastname: Nishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Takeda
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002738:Chloroquine / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D010084:Oxidation-Reduction; D010455:Peptides / Q000494:pharmacology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000032:analysis*; D014812:Vitamin K / Q000031:analogs & derivatives / Q000494:pharmacology; D024483:Vitamin K 3 / Q000031:analogs & derivatives*; D014909:Wheat Germ Agglutinins / Q000494:pharmacology
chemical_list: D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011768:Pyruvate Dehydrogenase Complex; D014909:Wheat Germ Agglutinins; C047279:insulin-stimulating peptide, human; D003208:Concanavalin A; D014812:Vitamin K; D012710:Serum Albumin, Bovine; D024483:Vitamin K 3; D002738:Chloroquine; D005947:Glucose; C024534:vitamin k5