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Titolo:
Effects of retinoids and thiazolidinediones on proliferation, insulin release, insulin mRNA, GLUT 2 transporter protein and mRNA of INS-1 cells
Autore:
Blumentrath, J; Neye, H; Verspohl, EJ;
Indirizzi:
Univ Munster, Dept Pharmacol, Inst Pharmaceut Chem, D-48149 Munster, Germany Univ Munster Munster Germany D-48149 ceut Chem, D-48149 Munster, Germany
Titolo Testata:
CELL BIOCHEMISTRY AND FUNCTION
fascicolo: 3, volume: 19, anno: 2001,
pagine: 159 - 169
SICI:
0263-6484(200109)19:3<159:EORATO>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACID RECEPTOR-ALPHA; MESSENGER-RNA; GLUCOKINASE ACTIVITY; GLUCOSE-TRANSPORTER; GENE-EXPRESSION; SECRETING CELLS; THYROID-HORMONE; RAT; DIFFERENTIATION; ISLETS;
Keywords:
retinoids; rosiglitazone; INS-1 cells; insulin release; cell proliferation; GLUT 2;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Verspohl, EJ Univ Munster, Dept Pharmacol, Inst Pharmaceut Chem, Hittorfstr 58-62, D-48149 Munster, Germany Univ Munster Hittorfstr 58-62 Munster Germany D-48149 ermany
Citazione:
J. Blumentrath et al., "Effects of retinoids and thiazolidinediones on proliferation, insulin release, insulin mRNA, GLUT 2 transporter protein and mRNA of INS-1 cells", CELL BIOC F, 19(3), 2001, pp. 159-169

Abstract

Both 9-cis-retinoic acid (9cRA) and all-trans-retinoic acid (ATRA) are active metabolites of vitamin A (retinol). There exists an interaction betweenretinoid receptors and peroxisome proliferator-activated receptors (PPAR gamma). To define their functions in an insulin secreting system the effectsof ATRA, 9cRA and the PPAR gamma agonist rosiglitazone on cell proliferation, insulin release and glucose transporter (GLUT) 2 of INS-1 cells were tested. Retinoic acid receptor (RAR-alpha and -gamma) and retinoid X receptor(RXR-alpha and -beta) proteins are present (immunoblots). Both 9cRA and ATRA inhibit INS-1 cell proliferation ([H-3]-thymidine assay) in a concentration dependent manner. Both 9cRA and ATRA increased insulin release, but only ATRA ralsed the GLUT 2 mRNA in a bell-shaped concentration response curveafter 48 h. The insulinotropic effect of one compound is not significantlysuperimposed by the other indicating that the same binding sites are used by 9cRA and ATRA. The acute and chronic effects of the PPAR gamma agonist rosiglitazone on insulin release were additionally determined since glita-zones act as transcription factors together with RXR agonists. At high concentrations (100 gm) rosiglitazone inhibited glucose (8.3 mm) stimulated insulin secretion (acute experiment over 60 min). Insulin secretion, however, was increased during a 24 h treatment at a concentration of 10 mum and again inhibited at 100 mum. Changes in preproinsulin mRNA expression were not observed. Rosiglitazone (100 Am) increased GLUT 2 mRNA paralleled by an increase of GLUT 2 protein, but only after 24 h of treatment. This data indicate that RAR and RXR mediate insulin release. The changes in GLUT 2 have no direct impact on insulin release; the inhibition seen at high concentrations of either compound is possibly the result of the observed inhibition of cellproliferation. Effects of rosiglitazone on preproinsulin mRNA and GLUT 2 (mRNA and protein) do not play a role in modulating insulin secretion. With the presence of an RXR receptor agonist the effect of rosiglitazone on insulin release becomes stimulatory. Thus the effects of RAR-, RXR agonists androsiglitazone depend on their concentrations, the duration of their presence and are due to specific interactions. Copyright (C) 2001 John Wiley & Sons, Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 11:45:56