Abscisic Acid Is an Endogenous Stimulator of Insulin Release from Human Pancreatic Islets with Cyclic ADP Ribose as Second Messenger*
- Santina Bruzzone‡§,
- Nicoletta Bodrato‡,
- Cesare Usai¶,
- Lucrezia Guida‡§,
- Iliana Moreschi‡,
- Rita Nano∥,
- Barbara Antonioli∥,
- Floriana Fruscione‡§,
- Mirko Magnone‡§,
- Sonia Scarf쇧,
- Antonio De Flora‡ and
- Elena Zocchi‡§,1
- ‡Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV/1, 16132 Genova, §Advanced Biotechnology Center, Largo Rosanna Benzi 1, 16132 Genova, ¶Institute of Biophysics, Consiglio Nazionale delle Ricerche, Via De Marini 6, 16149 Genova, and ∥Islet Processing Facility, S. Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy
- ↵1 To whom correspondence should be addressed: Dept. of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV/1, 16132 Genova, Italy. Tel.: 390103538158; Fax: 39010354415; E-mail: ezocchi{at}unige.it.
Abstract
Abscisic acid (ABA) is a plant stress hormone recently identified as an endogenous pro-inflammatory cytokine in human granulocytes. Because paracrine signaling between pancreatic β cells and inflammatory cells is increasingly recognized as a pathogenetic mechanism in the metabolic syndrome and type II diabetes, we investigated the effect of ABA on insulin secretion. Nanomolar ABA increases glucose-stimulated insulin secretion from RIN-m and INS-1 cells and from murine and human pancreatic islets. The signaling cascade triggered by ABA in insulin-releasing cells sequentially involves a pertussis toxin-sensitive G protein, cAMP overproduction, protein kinase A-mediated activation of the ADP-ribosyl cyclase CD38, and cyclic ADP-ribose overproduction. ABA is rapidly produced and released from human islets, RIN-m, and INS-1 cells stimulated with high glucose concentrations. In conclusion, ABA is an endogenous stimulator of insulin secretion in human and murine pancreatic β cells. Autocrine release of ABA by glucose-stimulated pancreatic β cells, and the paracrine production of the hormone by activated granulocytes and monocytes suggest that ABA may be involved in the physiology of insulin release as well as in its dysregulation under conditions of inflammation.
Footnotes
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↵* This work was supported in part by grants from Regione Liguria, from the Associazione Italiana per la Ricerca sul Cancro, from the Italian Ministry of Education, University and Scientific Research Grants MIUR-PRIN 2005, MIUR FIRB RBAUO19A3C, MIUR FIRB RBNE01ERXR, MIUR FIRB RBLA039LSF, and MIUR FIRB RBIP06LSS2, and the University of Genova and Fondazione Cassa di Risparmio di Genova e Imperia. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Received April 3, 2008.
- Revision received August 14, 2008.
- The American Society for Biochemistry and Molecular Biology, Inc.
