Di Marzo Vincenzo, Piscitelli Fabiana, Mechoulam Raphael
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei 34 Comprensorio Olivetti, 80078, Pozzuoli, NA, Italy.
Handb Exp Pharmacol. 2011(203):75-104. doi: 10.1007/978-3-642-17214-4_4.
The cannabinoid receptors for Δ(9)-THC, and particularly, the CB(1) receptor, as well as its endogenous ligands, the endocannabinoids anandamide and 2-arachidonoylglycerol, are deeply involved in all aspects of the control of energy balance in mammals. While initially it was believed that this endocannabinoid signaling system would only facilitate energy intake, we now know that perhaps even more important functions of endocannabinoids and CB(1) receptors in this context are to enhance energy storage into the adipose tissue and reduce energy expenditure by influencing both lipid and glucose metabolism. Although normally well controlled by hormones and neuropeptides, both central and peripheral aspects of endocannabinoid regulation of energy balance can become dysregulated and contribute to obesity, dyslipidemia, and type 2 diabetes, thus raising the possibility that CB(1) antagonists might be used for the treatment of these metabolic disorders. On the other hand, evidence is emerging that some nonpsychotropic plant cannabinoids, such as cannabidiol, can be employed to retard β-cell damage in type 1 diabetes. These novel aspects of endocannabinoid research are reviewed in this chapter, with emphasis on the biological effects of plant cannabinoids and endocannabinoid receptor antagonists in diabetes.
Δ(9)-四氢大麻酚的大麻素受体，尤其是CB(1)受体，以及其内源性配体——内源性大麻素花生四烯乙醇胺和2-花生四烯酸甘油酯，在哺乳动物能量平衡控制的各个方面都有着深入的参与。虽然最初人们认为这种内源性大麻素信号系统只会促进能量摄入，但我们现在知道，在这种情况下，内源性大麻素和CB(1)受体可能更重要的功能是通过影响脂质和葡萄糖代谢来增强能量储存到脂肪组织中，并减少能量消耗。尽管内源性大麻素对能量平衡的调节在中枢和外周方面通常都受到激素和神经肽的良好控制，但仍可能失调并导致肥胖、血脂异常和2型糖尿病，因此增加了CB(1)拮抗剂可能用于治疗这些代谢紊乱的可能性。另一方面，越来越多的证据表明，一些非精神活性植物大麻素，如大麻二酚，可用于延缓1型糖尿病中的β细胞损伤。本章将对这些内源性大麻素研究的新方面进行综述，重点是植物大麻素和内源性大麻素受体拮抗剂在糖尿病中的生物学效应。
