Gilon Patrick
Pôle d'endocrinologie, diabète et nutrition, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Hippocrate 55, B1.55.06, 1200, Brussels, Belgium.
Diabetologia. 2016 Sep;59(9):1855-9. doi: 10.1007/s00125-016-4052-y. Epub 2016 Jul 15.
Type 2 diabetes is characterised by chronic hyperglycaemia and its incidence is highly increased by exaggerated food consumption. It results from a lack of insulin action/production, but growing evidence suggests that it might also involve hyperglucagonaemia and impaired control of glucose homeostasis by the brain. In recent years, the cocaine and amphetamine-regulated transcript (CART) peptides have generated a lot of interest in the battle against obesity because, via the brain, they exert anorexic effects and they increase energy expenditure. They are also localised, outside the brain, in discrete regions of the body and play a hormonal role in controlling various functions. In this issue of Diabetologia, the Wierup group (doi: 10.1007/s00125-016-4020-6 ) shows that CART peptides are expressed heterogeneously in islet cells of various species, including humans, and that their expression is upregulated in diabetes. The authors also shine a spotlight on some interesting effects of CART peptides on islet function, including stimulation of insulin secretion and inhibition of glucagon release. CART peptides would thus be at the centre of a cooperation between the brain and the endocrine pancreas to control glucose homeostasis. Although the mechanisms of action of CART peptides remain enigmatic because no specific receptor for these peptides has so far been discovered, their potential therapeutic use is evident and represents a new challenge for future research.
2型糖尿病的特征是慢性高血糖,过度饮食会使其发病率大幅上升。它是由胰岛素作用/分泌不足引起的,但越来越多的证据表明,它可能还涉及高胰高血糖素血症以及大脑对葡萄糖稳态的控制受损。近年来,可卡因和苯丙胺调节转录物(CART)肽在对抗肥胖的斗争中引起了广泛关注,因为它们通过大脑发挥厌食作用并增加能量消耗。它们在大脑之外的身体离散区域也有分布,并在控制各种功能中发挥激素作用。在本期《糖尿病学》中,维鲁普团队(doi: 10.1007/s00125-016-4020-6)表明,CART肽在包括人类在内的各种物种的胰岛细胞中呈异质性表达,并且在糖尿病中其表达会上调。作者还聚焦了CART肽对胰岛功能的一些有趣作用,包括刺激胰岛素分泌和抑制胰高血糖素释放。因此,CART肽可能处于大脑与内分泌胰腺合作以控制葡萄糖稳态的核心位置。尽管由于迄今为止尚未发现这些肽的特异性受体,CART肽的作用机制仍然成谜,但其潜在的治疗用途是显而易见的,这也为未来的研究带来了新的挑战。