下丘脑血糖感应系统缺陷与2型糖尿病的关系

Association between hypothalamic glucose-sensing system dysfunction and type 2 diabetes mellitus

到目前为止,中枢神经系统在正常葡萄糖稳态和2型糖尿病中所起的作用仍未阐明。但是越来越多的证据表明,中枢神经系统某些区域(如下丘脑)也存在葡萄糖感应系统,与胰腺一样,该系统也能感知和响应循环血液中葡萄糖水平的变化。下丘脑血糖感应系统主要包括葡萄糖刺激性神经元及葡萄糖抑制性神经元,分别在低血糖及高血糖时被激活。在低血糖时,为了保证大脑的葡萄糖供应,该血糖感应系统被激活从而迅速作用在外周靶器官,以抑制胰岛素分泌并上调胰高血糖素分泌,进而升高血糖,该反应即低血糖对抗神经回路反应(CRR)。而在遗传及环境因素的作用下,如果下丘脑感应葡萄糖的能力受损,导致CRR的血糖调定点上调,将促进2型糖尿病的发生。越来越多的临床前证据也表明,通过恢复大脑感知血糖水平功能的治疗措施,可用于治疗2型糖尿病。然而,下丘脑葡萄糖感应系统的细胞内机制仍未完全阐明,有待进一步研究证实。

Until now,roles of central nervous system in both normal glucose homeostasis and in type 2 diabetes mellitus remains poorly understood.Growing evidence indicates that there is glucose sensing system in selective central nervous system areas,such as the hypothalamus.Like the pancreas,hypothalamus is equipped to sense and respond to changes in the circulating glucose level.hypothalamic glucose sensing system mainly includes glucose stimulating neurons and glucose inhibitory neurons,which are activated at hypoglycemia and hyperglycemia respectively.In case of hypoglycemia,in order to ensure the energy supply to the brain,the glucose sensing system is activated quickly by acting on the peripheral target organs to inhibit insulin secretion and up regulate glucagon secretion,so as to increase blood glucose.This response is called counterregulatory responses(CRRs)to hypoglycemia.Under certain circumference of genetic and environmental factors,if the ability of the hypothalamus to sense glucose level is impaired,the set-point of CRR will be increased which then promote the occurrence of type 2 diabetes mellitus.This perspective is strengthened by growing preclinical evidence that in type 2 diabetes mellitus the defended level of blood glucose can be restored to normal by therapies that restore the brain's ability to properly sense the circulating glucose level.However,the underlying intracellular mechanisms of glucose sensing in the hypothalamus remain further studies.