Uncoupling protein 2 regulates reactive oxygen species formation in islets and influences susceptibility to diabetogenic action of streptozotocin
Uncoupling protein 2 regulates reactive oxygen species formation in islets and influences susceptibility to diabetogenic action of streptozotocin
复制标题
DOI：
10.1677/joe-09-0117
复制
发表时间：
2009-10-01
影响因子：
4
通讯作者：
Wheeler, Michael B.
中科院分区：
文献类型：
--
作者：
Lee, Simon C.;Robson-Doucette, Christine A.;Wheeler, Michael B.
目前，解偶联蛋白-2（UCP 2）在胰岛中的生理功能及其在糖尿病发生发展中的作用仍存在很大争议。为了进一步研究UCP 2对糖尿病发展的影响，我们使用链脲佐菌素（STZ）在野生型（WT）和UCP 2敲除（UCP 2KO）小鼠中实验性产生糖尿病。虽然多次低剂量STZ注射在WT和UCP 2KO中均导致14天内的高血糖症发展（nice），但我们发现在UCP 2KO中高血糖症的发展明显不那么严重（nice.测量胰岛素和胰高血糖素分泌（体外），以及它们的血浆浓度（体内），表明UCP 2缺乏显示胰岛素分泌增强，但α细胞功能受损。尽管暴露于STZ后胰岛素分泌减少，但胰高血糖素分泌减弱，这共同导致UCP 2KO小鼠中不太严重的高血糖症发展。进一步的实验显示，UCP 2缺陷的α-和β-细胞在STZ应用之前具有比WT长期更高的细胞活性氧（ROS）水平，这与增加的基础β-和α-细胞质量相关。总之，我们认为UCP 2缺乏导致的慢性ROS信号传导增加有助于增强β细胞功能和损害α细胞功能，导致STZ诱导的高血糖症发展减弱。内分泌学杂志（2009）203，33-43
Currently, the physiological function of uncoupling protein-2 (UCP2) in pancreatic islets and its role in the development of diabetes is a (natter of great debate. To further investigate the impact of UCP2 on diabetes development, we used streptozotocin (STZ) to experimentally generate diabetes in both wild-type (WT) and UCP2-knockout (UCP2KO) mice. While multiple low-dose STZ injections led to hyperglycemia development over a 14-day period in both WT and UCP2KO (nice, we found the development of hyperglycemia to be significantly less severe in the UCP2KO (nice. Measurement of insulin and glucagon secretion (in vitro), as well as their plasma concentrations (in vivo), indicated that UCP2-deficiency showed enhanced insulin secretion but impaired alpha-cell function. Glucagon secretion was attenuated, despite reduced insulin secretion after exposure to STZ, which together contributed to less severe hyperglycemia development in UCP2KO mice. Further experimentation revealed that UCP2-deficient alpha- and beta-cells had chronically higher cellular reactive oxygen species (ROS) levels than the WT prior to STZ application, which correlated with increased basal beta- and alpha-cell mass. Overall, we suggest that increased chronic ROS signaling as a result of UCP2-deficiency contributes to enhanced beta-cell function and impairment of alpha-cell function, leading to an attenuation of STZ-induced hyperglycemia development. Journal of Endocrinology (2009) 203, 33-43