title: Reciprocal interaction among gasotransmitters in isolated pancreatic β-cells.
abstract: We aimed to elucidate the interplay among the three well-known gas molecules, nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), and their effects on intracellular Ca(2+) concentration ([Ca(2+)]i) and insulin secretion in rat pancreatic β-cells. Immunofluorescence studies demonstrated the expression of constitutive enzymes that are responsible for the production of NO, CO and H2S. CO and H2S increased NO production as indicated by the increase in diaminofluorescein-2 triazole fluorescence. NO and CO induced an elevation in the sulfane sulfur pool and concomitantly H2S production. The NO- and CO-induced H2S production was partially inhibited by hypotaurine, an H2S scavenger. NO and H2S produced CO production as revealed by a myoglobin assay. A calmodulin antagonist in the absence of extracellular Ca(2+) significantly attenuated NO and H2S production. NO and CO induced a [Ca(2+)]i increase mainly via Ca(2+) release from internal stores; however, H2S induced a [Ca(2+)]i increase via the influx of extracellular Ca(2+). NO dose-dependently stimulated basal insulin release but CO dose-dependently inhibited it. H2S showed an insignificant effect on basal insulin secretion from freshly isolated pancreatic islets. Herein, we address for the first time the reciprocal and synergistic relation among gasotransmitters with diverse effects on basal insulin secretion that regulate β-cells functions and homeostasis.
authors.affiliation: Laboratory of Physiology, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan; Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt.
authors.forename: Amira
authors.initials: A
authors.lastname: Moustafa
authors.affiliation: Laboratory of Physiology, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. Electronic address: habara@vetmed.hokudai.ac.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Habara
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002248:Carbon Monoxide / Q000378:metabolism*; D064426:Gasotransmitters / Q000096:biosynthesis*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D064426:Gasotransmitters; D009569:Nitric Oxide; D002248:Carbon Monoxide; D002118:Calcium; D006862:Hydrogen Sulfide
keywords: Carbon monoxide; Hydrogen sulfide; Insulin; Intracellular Ca(2+); Nitric oxide