Critical Roles of Carbon Monoxide and Nitric Oxide in Ca2+ Signaling for Insulin Secretion in Pancreatic Islets

Antioxidants & Redox Signaling
Faiz Ur RahmanUh-Hyun Kim

Abstract

Glucagon-like peptide-1 (GLP-1) increases intracellular Ca2+ concentrations, resulting in insulin secretion from pancreatic β-cells through the sequential production of Ca2+ mobilizing messengers nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose (cADPR). We previously found that NAADP activates the neuronal type of nitric oxide (NO) synthase (nNOS), the product of which, NO, activates guanylyl cyclase to produce cyclic guanosine monophosphate (cGMP), which, in turn, induces cADPR formation. Our aim was to explore the relationship between Ca2+ signals and gasotransmitters formation in insulin secretion in β-cells upon GLP-1 stimulation. We show that NAADP-induced cGMP production by nNOS activation is dependent on carbon monoxide (CO) formation by heme oxygenase-2 (HO-2). Treatment with exogenous NO and CO amplifies cGMP formation, Ca2+ signal strength, and insulin secretion, whereas this signal is impeded when exposed to combined treatment with NO and CO. Furthermore, CO potentiates cGMP formation in a dose-dependent manner, but higher doses of CO inhibited cGMP formation. Our data with regard to zinc protoporphyrin, a HO inhibitor, and HO-2 knockdown, revealed that NO-induced cADPR formation and insuli...Continue Reading

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Citations

Aug 14, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Patrycja KaczaraStefan Chlopicki
Dec 11, 2020·Free Radical Research·Amr AliGuangdong Yang
Oct 23, 2020·Chemical Reviews·Christopher P HopperBinghe Wang
Jul 3, 2021·Metabolites·Marcello C LaurentiAdrian Vella
Nov 28, 2021·Journal of Biophotonics·Caleb LiebmanMichael Cho

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Methods Mentioned

BETA
gene knockdown
immunoprecipitation
enzyme-linked immunosorbent assay
ELISA
protein assay
transfection
enzyme-linked

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