title: Abscisic acid is an endogenous stimulator of insulin release from human pancreatic islets with cyclic ADP ribose as second messenger.
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 beta 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 beta cells. Autocrine release of ABA by glucose-stimulated pancreatic beta 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.
authors.affiliation: Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV/1, 16132 Genova, Italy.
authors.forename: Santina
authors.initials: S
authors.lastname: Bruzzone
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bodrato
authors.forename: Cesare
authors.initials: C
authors.lastname: Usai
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Guida
authors.forename: Iliana
authors.initials: I
authors.lastname: Moreschi
authors.forename: Rita
authors.initials: R
authors.lastname: Nano
authors.forename: Barbara
authors.initials: B
authors.lastname: Antonioli
authors.forename: Floriana
authors.initials: F
authors.lastname: Fruscione
authors.forename: Mirko
authors.initials: M
authors.lastname: Magnone
authors.forename: Sonia
authors.initials: S
authors.lastname: Scarfì
authors.forename: Antonio
authors.initials: A
authors.lastname: De Flora
authors.forename: Elena
authors.initials: E
authors.lastname: Zocchi
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000040:Abscisic Acid / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D036563:Cyclic ADP-Ribose / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D037342:Pertussis Toxin / Q000494:pharmacology; D051381:Rats
chemical_list: D007328:Insulin; D036563:Cyclic ADP-Ribose; D000040:Abscisic Acid; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D051997:ADP-ribosyl Cyclase 1