Effects of islet amyloid polypeptide (amylin) and calcitonin gene-related peptide (CGRP) on glucose metabolism in the rat.
In this study, we compared the effects of islet amyloid polypeptide (IAPP) and calcitonin gene-related peptide (CGRP) on glucose metabolism both in vivo and in vitro in the rat. Intravenous injection of rat CGRP caused a significant increase in plasma glucose concentration with a simultaneous increase in plasma insulin levels, whereas neither IAPP-NH2 nor IAPP-COOH had any effect. Moreover, intravenous infusion of CGRP decreased tolerance to intragastric administration of glucose (O-GTT) without altering plasma insulin levels, but again IAPPs had no effect. On the other hand, 125I-[Tyr0]rat CGRP specifically bound to the liver plasma membrane, and not only CGRP but also IAPP-NH2 dose-dependently displaced the specific binding of 125I-[Tyr0] CGRP, whereas IAPP-COOH had no effect. Conversely, CGRP as well as IAPP-NH2 but not IAPP-COOH evoked dose-dependent activation of adenylate cyclase in the membranes, and these effects were significantly inhibited by a CGRP receptor antagonist, human CGRP-I(8-37). However, neither CGRP nor IAPP-NH2 had any effect on glucose production in rat isolated hepatocytes. These results suggest that (1) IAPP-NH2 but not IAPP-COOH induces adenylate cyclase activation via CGRP receptors on rat liver plasma membranes, and (2) CGRP might not involve its action on the liver in the changes of glucose metabolism.
Morishita
T
T
Third Division Department of Medicine, Kobe University School of Medicine, Japan.
Yamaguchi
A
A
Yamatani
T
T
Nakamura
A
A
Arima
N
N
Yamashita
Y
Y
Nakata
H
H
Fujita
T
T
Chiba
T
T
D000682:Amyloid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood*; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D008112:Liver Glycogen; D005947:Glucose; D015740:Calcitonin Gene-Related Peptide