Gerozissis Kyriaki
Chercheur INSERM, UMR 7059 CNRS, University Paris 7, 2 place Jussieu, case 7126, 75251 Paris CEDEX 05, France.
Eur J Pharmacol. 2008 May 6;585(1):38-49. doi: 10.1016/j.ejphar.2008.01.050. Epub 2008 Feb 29.
The central nervous system is essential in maintaining energy and glucose homeostasis. In both animals and humans, efficient cerebral insulin signalling is a pivotal control element in these pathophysiological processes. The action of insulin in the brain is under a multilevel control via metabolic, endocrine and neural signals induced by nutrients, integrated mainly by the hypothalamus. Of particular interest is the interaction of insulin with the anabolic and catabolic neuroregulators. The anorexic peptides insulin, leptin and the neurotransmitter serotonin share common signalling pathways involved in food intake, in particular the insulin receptor substrate, phosphatidylinositol-3-kinase (PI3K) pathway. The dialogue of neurotransmitters and peptides via this signalling pathway is potentially of major importance in the pathophysiology of the brain in general and specifically in the regulation of feeding behaviour. At this time, a new concept in the aetiopathology of type 2 diabetes is immerging. This concept proposes that the combination of defective pancreatic beta-cell function and insulin resistance not only in classical insulin target tissues but in every tissue, contributes to the onset of the disease. It highlights the importance of the disruption of cerebral insulin signal transmission and its direct relation to metabolic diseases. Impaired brain insulin signalling, a link coupling obesity to diabetes, may be related to either genetic factors, or environmental factors such as stress, over or under-feeding and unbalanced diets: such factors may work either independently or in concert. Current approaches used for the prevention and treatment of type 2 diabetes are not adequately effective. Most of the anti-diabetic therapies induce many adverse effects, in particular obesity, and thus may initiate a vicious cycle of problems. In order to develop new, more efficient, preventive and therapeutic strategies for metabolic pathologies, there is an urgent need for increased understanding of the complexity of insulin signalling in the brain and on the interactive, central and peripheral effects of insulin.
中枢神经系统对于维持能量和葡萄糖稳态至关重要。在动物和人类中，有效的脑胰岛素信号传导是这些病理生理过程中的关键控制要素。胰岛素在大脑中的作用受到营养物质诱导的代谢、内分泌和神经信号的多级控制，主要由下丘脑整合。特别值得关注的是胰岛素与合成代谢和分解代谢神经调节剂的相互作用。厌食肽胰岛素、瘦素和神经递质血清素共享参与食物摄入的共同信号通路，特别是胰岛素受体底物、磷脂酰肌醇-3-激酶（PI3K）通路。一般而言，神经递质和肽通过该信号通路的对话在大脑病理生理学中可能具有重要意义，特别是在进食行为的调节方面。此时，2型糖尿病病因病理学中的一个新概念正在浮现。这个概念提出，胰腺β细胞功能缺陷和胰岛素抵抗不仅存在于经典的胰岛素靶组织中，而且存在于每个组织中，这促成了该疾病的发生。它强调了脑胰岛素信号传导中断的重要性及其与代谢疾病的直接关系。脑胰岛素信号传导受损是肥胖与糖尿病之间的联系，可能与遗传因素或环境因素有关，如压力、过度或不足喂养以及不均衡饮食：这些因素可能单独起作用或共同起作用。目前用于预防和治疗2型糖尿病的方法效果并不理想。大多数抗糖尿病疗法会引发许多不良反应，特别是肥胖，因此可能引发问题的恶性循环。为了开发针对代谢疾病的新的、更有效的预防和治疗策略，迫切需要加深对大脑中胰岛素信号传导复杂性以及胰岛素的中枢和外周相互作用效应的理解。
