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）的周围内皮附属结构。我们之前已经证明，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，在糖尿病等病理条件下，周细胞在下丘脑胰岛素敏感性中的作用尚不清楚。高脂饮食诱导糖耐量受损的肥胖小鼠脑和脑微血管中亲环蛋白A （CypA）及其受体CD147的表达升高。生理条件下，周细胞的CypA释放量远高于其他血脑屏障构成细胞。TNF-a增加周细胞的CypA释放。TNF-a联合CypA治疗降低了下丘脑神经元的胰岛素敏感性。因此，周细胞和周细胞CypA可能参与中枢神经系统胰岛素抵抗。

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.