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Biochem Biophys Res Commun. 2012 Jun 22;423(1):13-8. doi: 10.1016/j.bbrc.2012.05.042. Epub 2012 May 15.

Blockade of β-cell K(ATP) channels by the endocannabinoid, 2-arachidonoylglycerol.

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Cellular Neurobiology Branch, Electrophysiology Research Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.


The endocannabinoid system has been demonstrated to be active in the pancreatic β-cell. However the effects of the endocannabinoids (ECs) on insulin secretion are not well defined and may vary depending on the metabolic state of the β-cell. Specifically it is not known whether the effects of the ECs occur by activation of the cannabinoid receptors or via their direct interaction with the ion channels of the β-cell. To begin to delineate the effects of ECs on β-cell function, we examined how the EC, 2-AG influences β-cell ion channels in the absence of glucose stimulation. The mouse insulinoma cell line R7T1 was used to survey the effects of 2-AG on the high voltage activated (HVA) calcium, the delayed rectifier (K(v)), and the ATP-sensitive K (K(ATP)) channels by whole cell patch clamp recording. At 2mM glucose, 2-AG inhibited the HVA calcium (the majority of which are L-type channels), K(v), and K(ATP) channels. The channel exhibiting the most sensitivity to 2-AG blockade was the K(ATP) channel, where the IC(50) for 2-AG was 1 μM. Pharmacological agents revealed that the blockade of all these channels was independent of cannabinoid receptors. Our results provide a mechanism for the previous observations that CB1R agonists increase insulin secretion at low glucose concentrations through CB1R independent blockade of the K(ATP) channel.

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