Abscisic acid is an endogenous stimulator of insulin release from human pancreatic islets with cyclic ADP ribose as second messenger.
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.
Bruzzone
Santina
S
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV/1, 16132 Genova, Italy.
Bodrato
Nicoletta
N
Usai
Cesare
C
Guida
Lucrezia
L
Moreschi
Iliana
I
Nano
Rita
R
Antonioli
Barbara
B
Fruscione
Floriana
F
Magnone
Mirko
M
Scarfì
Sonia
S
De Flora
Antonio
A
Zocchi
Elena
E
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
D007328:Insulin; D036563:Cyclic ADP-Ribose; D000040:Abscisic Acid; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D051997:ADP-ribosyl Cyclase 1