Proadrenomedullin N-terminal 20 peptide (PAMP) elevates blood glucose levels via bombesin receptor in mice.
We found a potent hyperglycemic effect of proadrenomedullin N-terminal 20 peptide (PAMP) after intra-third cerebroventricular administration at a dose of 10 nmol in fasted mice. PAMP has four homologous residues with bombesin (BN), a hyperglycemic peptide. PAMP showed affinity for gastrin-releasing peptide preferring receptor (GRP-R) and neuromedin B preferring receptor. The PAMP-induced hyperglycemic effect was inhibited by [D-Phe(6), Leu-NHEt(13), des-Met(14)]-BN (6-14), GRP-R specific antagonist, indicating that the hyperglycemic effect is mediated at least in part via GRP-R. Furthermore, pretreatment of alpha-adrenergic blocker inhibited the PAMP-induced hyperglycemia and hyperglucagonemia, suggesting that the increase of glucagon secretion through alpha-adrenergic activation is involved in this hyperglycemic effect of PAMP.
Ohinata
K
K
Department of Functional Food Resources, Research Institute for Food Science, Kyoto University, Gokasho Uji, Kyoto, Japan.
Inui
A
A
Asakawa
A
A
Wada
K
K
Wada
E
E
Yoshikawa
M
M
D016475:3T3 Cells; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D053607:Adrenomedullin; D000818:Animals; D001667:Binding, Competitive; D001786:Blood Glucose / Q000187:drug effects*; D001839:Bombesin / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood; D008297:Male; D008566:Membranes / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides; D010646:Phentolamine / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D018004:Receptors, Bombesin; D014280:Triglycerides; D053607:Adrenomedullin; D002784:Cholesterol; D001839:Bombesin; D010646:Phentolamine