Involvement of pericytes-derived cyclophilin A in the development of insulin resistanse in the brain

微血管中的脑周细胞是血脑屏障(BBB)的内皮周围附属结构。我们先前已经证明，在生理条件下，周细胞通过可溶性因子增加下丘脑神经元的胰岛素敏感性。然而，在糖尿病(DM)等病理条件下，周细胞在下丘脑胰岛素敏感性中的作用仍然不清楚。高脂饮食诱导的糖耐量减低肥胖小鼠脑和脑微血管中亲环素A及其受体CD147的表达增加。在生理条件下，周细胞释放的CypA远高于其他构成血脑屏障的细胞。肿瘤坏死因子-α促进周细胞释放CypA。联合应用肿瘤坏死因子-α和CypA可降低下丘脑神经元的胰岛素敏感性。因此，周细胞和周细胞CypA可能参与了中枢神经系统的胰岛素抵抗。

Brain pericytes in the microvasculature are periendothelial accessory structures of the blood-brain barrier (BBB). We previously demonstrated that pericytes increase insulin sensitivity in the hypothalamic neurons through soluble factors under the physiological conditions. However, under the pathological conditions such as diabetes mellitus (DM), a role of pericytes in hypothalamic insulin sensitivity remained obscure. The expression of cyclophilin A (CypA) and its receptor, CD147 in the brain and brain microvessels were increased in the obese mice with impaired glucose tolerance induced by high fat diet. CypA release from pericytes was much higher than that from other BBB-constituting cells under the physiological conditions. TNF-a increased CypA release from pericytes. The treatment of TNF-a combined with CypA decreased insulin sensitivity in the hypothalamic neurons. Therefore, pericytes and pericytal CypA could be involved in insulin resistance in the central nervous system.