肽基脯氨酰异构酶B在2型糖尿病β细胞内胰岛素原稳态失衡中作用的研究

The perturbation of Proinsulin Homeostasis is a new conception in beta cell function disorder, which refers to the abnormality of insulin release and beta cell failure caused by the imbalance of natively folded proinsulin monomers and non-natively (incompletely/incorrectly) folded proinsulin polypeptides in diabetic beta cell. In previous study, we found that the peptidyl prolyl isomerase B (PPIB) played a key role in the cause of PIHO maintenance, but it is not clear that the expression of PPIB in type 2 diabetic beta cells, and the influence of PPIB to the formation of natively folded proinsulin monomers, insulin release function, as well as beta cell apoptosis. We will investigate the expression level of proinsulin formation related PPIB，and the relation of the formation of natively folded proinsulin monomers, insulin release function, as well as beta cell apoptosis in type 2 diabetic beta cells, the influence of PPIB to PIHO in beta cells through inhibiting the expression of PPIB gene and protein.

胰岛素原稳态（PIHO）失衡是针对糖尿病β细胞内胰岛素原天然折叠单体与非天然折叠多肽比例失调，所致胰岛素释放异常、β细胞功能衰竭而提出的新观点。我们在先期研究中，发现肽基脯氨酰异构酶B（PPIB）可能在糖尿病β细胞内维持PIHO过程中扮演着重要的角色，但对于其在2型糖尿病β细胞内表达的特点，及其对胰岛素天然折叠单体形成、胰岛素释放和β细胞凋亡的影响仍不明确。.本研究将以肥胖型db/db 小鼠作为2型糖尿病模型，探讨2型糖尿病β细胞内参与胰岛素原折叠单体形成的PPIB表达水平及其与胰岛素原天然折叠单体形成、胰岛素释放和β细胞凋亡之间的关系；同时通过抑制PPIB基因及蛋白表达来反证β细胞内PPIB对PIHO的影响，为今后更深入的研究铺垫基础。

胰岛素原稳态（Proinsulin Homeostasis, Aka, PIHO）失衡是针对糖尿病β细胞内胰岛素原天然折叠单体与非天然折叠多肽比例失调，所致胰岛素释放异常、β细胞功能衰竭而提出的新观点。我们在先期研究中，发现肽基辅氨酰异构酶B（PPIB）可能在糖尿病β细胞内维持PIHO过程中扮演着一定的角色，但对于其在2型糖尿病β细胞内表达的特点，及其对胰岛素天然折叠单体形成、胰岛素释放和β细胞凋亡的影响仍不明确。.本研究以肥胖型db/db小鼠作为2型糖尿病模型，探讨2型糖尿病β细胞内参与胰岛素原折叠单体形式的PPIB表达水平及其与胰岛素原天然折叠单体形成、胰岛素释放.和β细胞凋亡之前的关系；同时通过抑制PPIB基因及蛋白表达来反证β细胞内PPIB对PIHO的影响，为今后更深入的研究铺垫基础。