BETA CELL PHYSIOLOGY & BIOCHEMISTY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 通过之前与生物电流研究中心的科学家的合作，我们证明了pH在介导四氧嘧啶对胰岛毒性中的作用。自参照型氧敏电极是实时研究胰岛功能(耗氧量)的理想方法。众所周知，胰岛的耗氧量与胰岛素的释放密切相关。四氧嘧啶的稳定性和毒性受pH的影响。我们已经证实，葡萄糖的存在抑制了胰岛中的四氧嘧啶毒性。这种作用是由于葡萄糖代谢引起的细胞内碱化。我们建议通过研究氧化应激在胰岛功能中的作用来扩大这种合作。先前的研究表明，氧化应激可以对胰岛功能产生积极和消极的影响。虽然过氧化氢酶和超氧化物歧化酶的表达可以阻断链脲佐菌素诱导的胰岛毒性，但过氧化氢似乎在葡萄糖刺激的信号转导中也发挥了重要作用。胰岛区分有害的和有益的氧化应激的机制尚不清楚。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Through previous collaborations with scientists at the Biocurrents Research Center, we demonstrated the role of pH in mediating the toxicity of alloxan in pancreatic beta islets. Self-referencing oxygen sensing electrodes have proven to be an ideal way to study isolated islet function (oxygen consumption) in real time. It is well recognized that oxygen consumption by islets is strongly correlated with insulin release. Alloxan stability and thus toxicity is affected by pH. We have established that presence of glucose dampens alloxan toxicity in pancreatic islets. This effect is due to the intracellular alkalinization, caused by glucose metabolism. We propose to expand this collaboration by studying the role of oxidative stress in beta islet function. Previous studies have demonstrated that oxidative stress can positively and negatively impact beta islet function. While streptozotocin-induced islet toxicity can be blocked by catalase and superoxide dismutase expression, hydrogen peroxide also seems to play an important role in signaling in response to glucose stimulation. The mechanisms by which islets differentiate between harmful and helpful oxidative stress are not clear.