BETA CELL PHYSIOLOGY & BIOCHEMISTY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 通过之前与Biocurrents研究中心的科学家的合作，我们证明了pH在介导四氧嘧啶在胰岛β细胞中的毒性中的作用。自参考氧传感电极已被证明是一种理想的方式来研究孤立的胰岛功能（耗氧量）在真实的时间。 众所周知，胰岛的氧消耗与胰岛素释放密切相关。四氧嘧啶的稳定性和毒性受pH值的影响。我们已经确定，葡萄糖的存在抑制四氧嘧啶在胰岛中的毒性。 这种效应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β胰岛功能中的作用来扩大这种合作。 以前的研究已经证明，氧化应激可以积极和消极地影响β胰岛功能。 虽然链脲佐菌素诱导的胰岛毒性可以通过过氧化氢酶和超氧化物歧化酶表达来阻断，但过氧化氢似乎也在响应葡萄糖刺激的信号传导中起重要作用。 胰岛区分有害和有益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.