Abscisic Acid Is an Endogenous Stimulator of Insulin Release from Human Pancreatic Islets with Cyclic ADP Ribose as Second Messenger

LANCL2 Is Necessary for Abscisic Acid Binding and Signaling in Human Granulocytes and in Rat Insulinoma Cells

“…5A, gray trace) (Fig. 5C), similarly to what already observed in human granulocytes (16) and in human and rat insulin-releasing cells (19). Sensitivity of the [cAMP] i increase to PTX points to G i as the G-protein coupled to LANCL2: activation of adenylic cyclase (AC) by G i has been reported to occur via a synergistic mechanism involving (i) interaction of AC with the ␤␥ subunits released from activated G i and (ii) AC phosphorylation by protein kinase C (33).…”

“…Cell Culture-The rat insulinoma RIN-m cell line was obtained from ATCC and cultured as described previously (19). The rat insulinoma cell line INS-1 was kindly provided by Prof. F. Beguinot (Federico II University of Napoli, Italy) and cultured in the same medium as RIN-m cells, supplemented with 50 M 2-mercaptoethanol.…”

“…Pathway-Nanomolar ABA (1-10 nM) stimulates insulin release from human and murine pancreatic ␤ cells and from RIN-m and INS-1 cells, and this effect is abrogated by PTX, by a protein kinase A-specific inhibitor preventing CD38 phosphorylation, by the cADPR antagonists 8-Br-cADPR and ryanodine and by the intracellular Ca 2ϩ chelator EGTA-AM (19). ABA triggers a steady, concentration-dependent increase of the [Ca 2ϩ ] i in RIN-m and INS-1 cells (Fig.…”

“…Scatchard plot analysis of [ 3 H]ABA binding demonstrated presence of both high and low affinity ABA binding sites (K d 11 nM and 500 M, respectively) on human granulocytes (16). Most recently, nanomolar ABA has been shown to stimulate insulin secretion by human and murine pancreatic ␤ cells and by rat insulinoma cell lines through a signaling pathway similar to the one described in human granulocytes (19). The autocrine release of ABA from glucose-stimulated human and rodent insulin-releasing cells, together with the fact that ABA is also produced by activated inflammatory cells, granulocytes (16), and monocytes (20), suggests that this hormone may contribute to the network of cytokine signals exchanged between inflammatory cells and pancreatic ␤ cells, which is increasingly recognized as a fundamental mechanism in the development of the metabolic syndrome and type II diabetes (21)(22)(23)(24).…”

Structural insights into ABA perception and signalling: structure of ABA receptor PYR1

“…Bassaganya-Riera et al (2011) have also demonstrated a role of ABA in modulation of inflammatory responses. More recently, ABA has been suggested to stimulate broader physiological responses in mammals, including insulin release in pancreatic islets Bruzzone et al 2008;Bodrato et al 2009;Magnone et al 2009). These evidences suggest the possibility that the origin of this hormone was prior to the great division of kingdoms.…”