Abstract
Pharmacological treatment of pancreatic β cells targeting cannabinoid receptors 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 recently developed photo-releasable endocannabinoid 2-arachidonoylglycerol 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 functional role of CB1 and CB2 acting in concert as a compensator/attenuator switch for regulating β cell excitability.
Keywords: 2-AG, caged endocannabinoid, calcium signaling, cannabinoid receptors, fluorescence, insulin secretion, photolysis; β-cell
Copyright © 2020. Published by Elsevier Ltd.
Conflict of interest statement
Declaration of Interests The authors declare no competing interest.
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