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Titolo:
PAC1 receptor-deficient mice display impaired insulinotropic response to glucose and reduced glucose tolerance
Autore:
Jamen, F; Persson, K; Bertrand, G; Rodriguez-Henche, N; Puech, R; Bockaert, J; Ahren, B; Brabet, P;
Indirizzi:
CNRS, UPR 9023, F-34094 Montpellier 5, France CNRS Montpellier France 5CNRS, UPR 9023, F-34094 Montpellier 5, France Univ Lund, Malmo Univ Hosp, Dept Med, Malmo, Sweden Univ Lund Malmo Sweden v Lund, Malmo Univ Hosp, Dept Med, Malmo, Sweden
Titolo Testata:
JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 9, volume: 105, anno: 2000,
pagine: 1307 - 1315
SICI:
0021-9738(200005)105:9<1307:PRMDII>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE INTESTINAL POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE-1; PERFUSED RAT PANCREAS; ADENYLATE-CYCLASE; SIGNAL-TRANSDUCTION; STIMULATES INSULIN; BINDING-SITES; ISLET CELLS; BETA-CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Brabet, P CNRS, UPR 9023, 141 Rue Cardonille, F-34094 Montpellier 5, France CNRS 141 Rue Cardonille Montpellier France 5 tpellier 5, France
Citazione:
F. Jamen et al., "PAC1 receptor-deficient mice display impaired insulinotropic response to glucose and reduced glucose tolerance", J CLIN INV, 105(9), 2000, pp. 1307-1315

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a ubiquitousneuropeptide of the vasoactive intestinal peptide (VIP) family that potentiates glucose-stimulated insulin secretion. Pancreatic beta cells express two PACAP receptor subtypes, a PACAP-preferring (PAC1) and a VIP-shared (VPAC2) receptor. We have applied a gene targeting approach to create a mouse lacking the PAC1 receptor (PAC1(-/-)). These mice were viable and normoglycemic, but exhibited a slight feeding hyperinsulinemia. In vitro, in the isolated perfused pancreas, the insulin secretory response to PACAP was reducedby 50% in PAC1(-/-) mice, whereas the response to VIP was unaffected. In vivo, the insulinotropic action of PACAP was also acutely reduced, and the peptide induced impairment of glucose tolerance after an intravenous glucoseinjection. This demonstrates that PAC1 receptor is involved in the insulinotropic action of the peptide. Moreover, PAC1(-/-) mice exhibited reduced glucose-stimulated insulin secretion in vitro and in vivo, showing that the PAC1 receptor is required to maintain normal. insulin secretory responsiveness to glucose. The defective insulinotropic action of glucose was associated with marked glucose intolerance after both intravenous and gastric glucose administration. Thus, these results are consistent with a physiological role for the PAC1 receptor in glucose homeostasis, notably during food intake.

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Documento generato il 19/09/20 alle ore 22:55:14