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.
Original language | English (US) |
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Pages (from-to) | 88-96.e3 |
Journal | Cell Chemical Biology |
Volume | 28 |
Issue number | 1 |
DOIs | |
State | Published - Jan 21 2021 |
Keywords
- 2-AG
- caged endocannabinoid
- calcium signaling
- cannabinoid receptors
- fluorescence
- insulin secretion
- photolysis
- β-cell
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Drug Discovery
- Clinical Biochemistry