RT Journal Article
T1 The cannabinoid CB1 receptor and mTORC1 signalling pathways interact to modulate glucose homeostasis in mice
A1 Bermúdez Silva, Francisco Javier
A1 Romero-Zerbo, Silvana Yanina
A1 Haissaguerre, Magalie
A1 Ruz-Maldonado, Inmaculada
A1 Lhamyani, Said
A1 El-Bekay, Rajaa
A1 Tabarin, Antoine
A1 Marsicano, Giovanni
A1 Cota, Daniela
K1 Insulina
AB The endocannabinoid system (ECS) is an intercellular signallingmechanism that is present in the islets of Langerhans and plays arole in the modulation of insulin secretion and expansion of the β-cellmass. The downstream signalling pathways mediating these effectsare poorly understood. Mammalian target of rapamycin complex 1(mTORC1) signalling is a key intracellular pathway involved inenergy homeostasis and is known to importantly affect thephysiology of pancreatic islets. We investigated the possiblerelationship between cannabinoid type 1 (CB1) receptor signallingand the mTORC1 pathway in the endocrine pancreas of mice byusing pharmacological analysis as well as mice genetically lackingthe CB1 receptor or the downstream target of mTORC1, the kinasep70S6K1. In vitro static secretion experiments on islets, westernblotting, and in vivo glucose and insulin tolerance tests wereperformed. The CB1 receptor antagonist rimonabant decreasedglucose-stimulated insulin secretion (GSIS) at 0.1 µM whileincreasing phosphorylation of p70S6K1 and ribosomal protein S6(rpS6) within the islets. Specific pharmacological blockade ofmTORC1 by 3 nM rapamycin, as well as genetic deletion ofp70S6K1, impaired the CB1-antagonist-mediated decrease inGSIS. In vivo experiments showed that 3 mg/kg body weightrimonabant decreased insulin levels and induced glucoseintolerance in lean mice without altering peripheral insulinsensitivity; this effect was prevented by peripheral administrationof low doses of rapamycin (0.1 mg/kg body weight), which increasedinsulin sensitivity. These findings suggest a functional interactionbetween the ECS and the mTORC1 pathway within the endocrinepancreas and at the whole-organism level, which could haveimplications for the development of new therapeutic approachesfor pancreatic β-cell diseases.
PB The Company of Biologists
YR 2016
FD 2016
LK https://hdl.handle.net/10630/32315
UL https://hdl.handle.net/10630/32315
LA eng
NO Francisco J. Bermudez-Silva, Silvana Y. Romero-Zerbo, Magalie Haissaguerre, Inmaculada Ruz-Maldonado, Said Lhamyani, Rajaa El Bekay, Antoine Tabarin, Giovanni Marsicano, Daniela Cota; The cannabinoid CB1 receptor and mTORC1 signalling pathways interact to modulate glucose homeostasis in mice. Dis Model Mech 1 January 2016; 9 (1): 51–61. doi: https://doi.org/10.1242/dmm.020750
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026