University of Lethbridge, Lethbridge, AB T1K3M4, Canada.
University of Lethbridge, Lethbridge, AB T1K3M4, Canada.
Trends Endocrinol Metab. 2022 Dec;33(12):828-849. doi: 10.1016/j.tem.2022.08.003. Epub 2022 Oct 21.
The number of people diagnosed with diabetes mellitus and its complications is markedly increasing worldwide, leading to a worldwide epidemic across all age groups, from children to older adults. Diabetes is associated with premature aging. In recent years, it has been found that peripheral overactivation of the endocannabinoid system (ECS), and in particular cannabinoid receptor 1 (CB1R) signaling, plays a crucial role in the progression of insulin resistance, diabetes (especially type 2), and its aging-related comorbidities such as atherosclerosis, nephropathy, neuropathy, and retinopathy. Therefore, it is suggested that peripheral blockade of CB1R may ameliorate diabetes and diabetes-related comorbidities. The use of synthetic CB1R antagonists such as rimonabant has been prohibited because of their psychiatric side effects. In contrast, phytocannabinoids such as cannabidiol (CBD) and tetrahydrocannabivarin (THCV), produced by cannabis, exhibit antagonistic activity on CB1R signaling and do not show any adverse side effects such as psychoactive effects, depression, or anxiety, thereby serving as potential candidates for the treatment of diabetes and its complications. In addition to these phytocannabinoids, cannabis also produces a substantial number of other phytocannabinoids, terpenes, and flavonoids with therapeutic potential against insulin resistance, diabetes, and its complications. In this review, the pathogenesis of diabetes, its complications, and the potential to use cannabinoids, terpenes, and flavonoids for its treatment are discussed.
全球范围内被诊断患有糖尿病及其并发症的人数显著增加,导致糖尿病在所有年龄段(从儿童到老年人)都呈世界性流行。糖尿病与过早衰老有关。近年来,人们发现内源性大麻素系统(ECS)的外周过度激活,尤其是大麻素受体 1(CB1R)信号,在胰岛素抵抗、糖尿病(尤其是 2 型糖尿病)及其与衰老相关的并发症(如动脉粥样硬化、肾病、神经病和视网膜病变)的进展中起着至关重要的作用。因此,有人提出外周阻断 CB1R 可能改善糖尿病及其相关并发症。由于其精神副作用,合成 CB1R 拮抗剂如利莫那班的使用已被禁止。相比之下,大麻产生的植物大麻素如大麻二酚(CBD)和四氢大麻酚(THCV)对 CB1R 信号具有拮抗活性,且没有表现出任何不良副作用,如精神活性作用、抑郁或焦虑,因此它们可作为治疗糖尿病及其并发症的潜在候选药物。除了这些植物大麻素外,大麻还产生大量其他具有治疗胰岛素抵抗、糖尿病及其并发症潜力的植物大麻素、萜烯和类黄酮。在这篇综述中,讨论了糖尿病的发病机制、其并发症以及使用大麻素、萜烯和类黄酮治疗糖尿病的潜力。