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Cannabinoid receptor agonists and antagonists stimulate insulin secretion from isolated human islets of Langerhans.
Diabetes Obes Metab. 2011 Oct; 13(10):903-10.DO

Abstract

AIMS

The role of cannabinoid receptors in human islets of Langerhans has not been investigated in any detail, so the current study examined CB1 and CB2 receptor expression by human islets and the effects of pharmacological cannabinoid receptor agonists and antagonists on insulin secretion.

METHODS

Human islets were isolated from pancreases retrieved from heart-beating organ donors. Messenger RNAs encoding human CB1 and CB2 receptors were amplified from human islet RNA by RT-PCR and receptor localization within islets was identified by immunohistochemistry. Dynamic insulin secretion from human islets perifused with buffers supplemented with CB1 and CB2 receptor agonists and antagonists was quantified by radioimmunoassay.

RESULTS

RT-PCR showed that both CB1 and CB2 receptors are expressed by human islets and immunohistochemistry indicated that receptor expression co-localized with insulin-expressing β-cells. Perifusion experiments using isolated human islets showed that insulin secretion was reversibly stimulated by both CB1 and CB2 receptor agonists, with CB1 receptor activation associated with increased basal secretion whereas CB2 receptors were coupled to initiation and potentiation of insulin secretion. Antagonists at CB1 (N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) and CB2 (N-(1,3-Benzodioxol-5-ylmethyl)-1,2-dihydro-7-methoxy-2-oxo-8-(pentyloxy)-3-quinoline carboxamide) receptors failed to inhibit the stimulatory effects of the respective agonists and, unexpectedly, reversibly stimulated insulin secretion.

CONCLUSIONS

These data confirm the expression of CB1 and CB2 receptors by human islets and indicate that both receptor subtypes are coupled to the stimulation of insulin secretion. They also implicate involvement of CB1/2 receptor-independent pathways in the antagonist-induced stimulatory effects.

Authors+Show Affiliations

Diabetes Research Group, Division of Diabetes & Nutritional Sciences, King's College London, London, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21564460

Citation

Li, C, et al. "Cannabinoid Receptor Agonists and Antagonists Stimulate Insulin Secretion From Isolated Human Islets of Langerhans." Diabetes, Obesity & Metabolism, vol. 13, no. 10, 2011, pp. 903-10.
Li C, Bowe JE, Huang GC, et al. Cannabinoid receptor agonists and antagonists stimulate insulin secretion from isolated human islets of Langerhans. Diabetes Obes Metab. 2011;13(10):903-10.
Li, C., Bowe, J. E., Huang, G. C., Amiel, S. A., Jones, P. M., & Persaud, S. J. (2011). Cannabinoid receptor agonists and antagonists stimulate insulin secretion from isolated human islets of Langerhans. Diabetes, Obesity & Metabolism, 13(10), 903-10. https://doi.org/10.1111/j.1463-1326.2011.01422.x
Li C, et al. Cannabinoid Receptor Agonists and Antagonists Stimulate Insulin Secretion From Isolated Human Islets of Langerhans. Diabetes Obes Metab. 2011;13(10):903-10. PubMed PMID: 21564460.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid receptor agonists and antagonists stimulate insulin secretion from isolated human islets of Langerhans. AU - Li,C, AU - Bowe,J E, AU - Huang,G C, AU - Amiel,S A, AU - Jones,P M, AU - Persaud,S J, PY - 2011/5/14/entrez PY - 2011/5/14/pubmed PY - 2011/12/13/medline SP - 903 EP - 10 JF - Diabetes, obesity & metabolism JO - Diabetes Obes Metab VL - 13 IS - 10 N2 - AIMS: The role of cannabinoid receptors in human islets of Langerhans has not been investigated in any detail, so the current study examined CB1 and CB2 receptor expression by human islets and the effects of pharmacological cannabinoid receptor agonists and antagonists on insulin secretion. METHODS: Human islets were isolated from pancreases retrieved from heart-beating organ donors. Messenger RNAs encoding human CB1 and CB2 receptors were amplified from human islet RNA by RT-PCR and receptor localization within islets was identified by immunohistochemistry. Dynamic insulin secretion from human islets perifused with buffers supplemented with CB1 and CB2 receptor agonists and antagonists was quantified by radioimmunoassay. RESULTS: RT-PCR showed that both CB1 and CB2 receptors are expressed by human islets and immunohistochemistry indicated that receptor expression co-localized with insulin-expressing β-cells. Perifusion experiments using isolated human islets showed that insulin secretion was reversibly stimulated by both CB1 and CB2 receptor agonists, with CB1 receptor activation associated with increased basal secretion whereas CB2 receptors were coupled to initiation and potentiation of insulin secretion. Antagonists at CB1 (N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) and CB2 (N-(1,3-Benzodioxol-5-ylmethyl)-1,2-dihydro-7-methoxy-2-oxo-8-(pentyloxy)-3-quinoline carboxamide) receptors failed to inhibit the stimulatory effects of the respective agonists and, unexpectedly, reversibly stimulated insulin secretion. CONCLUSIONS: These data confirm the expression of CB1 and CB2 receptors by human islets and indicate that both receptor subtypes are coupled to the stimulation of insulin secretion. They also implicate involvement of CB1/2 receptor-independent pathways in the antagonist-induced stimulatory effects. SN - 1463-1326 UR - https://www.unboundmedicine.com/medline/citation/21564460/abstract/Cannabinoid_receptor_agonists_and_antagonists_stimulate_insulin_secretion_from_isolated_human_islets_of_Langerhans_ L2 - https://doi.org/10.1111/j.1463-1326.2011.01422.x DB - PRIME DP - Unbound Medicine ER -