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Regulation of Calcium Oscillations in ß-Cells by Co-Activated Cannabinoid Receptors
21 Pages Posted: 19 May 2020 Publication Status: Published
More...Abstract
Pharmacological treatment of pancreatic β-cells targeting cannabinoid receptor 1 and 2 (CB1 and CB2) has been shown to result in significant effects on insulin release, possibly by modulating intracellular calcium levels ([Ca2+]i). It is unclear how the interplay of CB1 and CB2 affects insulin secretion. Here, we demonstrate by the use of highly specific receptor antagonists and the newly developed photo-releasable endocannabinoid 2-arachidonoylgylcerol (caged 2-AG, cg2-AG) that both receptors have counteracting effects on cytosolic calcium oscillations. We further show that both receptors are juxtaposed in a way that increases ([Ca2+]i) oscillations in silent β-cells but dampens them in active ones. This study highlights a new functional role of cannabinoid receptors 1 and 2 acting in concert as a compensator/attenuator switch for regulating β-cell excitability.
Keywords: signal transduction, insulin secretion, pancreatic islets, caged compounds, calcium oscillations
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