BETA CELL COMPENSATORY FACTORS IN INSULIN RESISTANCE - STUDIES IN PREGNANCY

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。 这项研究得到了GCRC学生奖的支持。它的重点是先前批准的内部审查委员会议定书(12681)的一个子项目。它侧重于该提案分项目4的一个方面。胰岛素抵抗(IR)是2型糖尿病和心血管疾病的众所周知的组成部分。然而，在怀孕等状态下，短期IR是一种必要的生理现象。胰岛素抵抗期间正常血糖水平的维持依赖于分泌胰岛素的β细胞增加其产量以克服胰岛素抵抗的能力。这项建议将研究胰岛素抵抗时胰岛素分泌代偿性增加的生理学。在IR期间，向β细胞发出的增加胰岛素分泌的信号并没有明确的定义；尽管被认为是葡萄糖，但有理由怀疑葡萄糖只是机制的一部分，如果可能的话。将利用妊娠自发性IR的生理现象，并将其与短期药物诱导IR的实验模型进行比较，研究替代信号--β细胞补偿因子(BCCF)的可能性。此外，蛋白质组学的初步研究将用于启动潜在新的BCCF分子的鉴定。了解β细胞对IR的补偿信号可能会为预防或治疗2型糖尿病带来新的治疗可能性。

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. This study is supported by a GCRC student award. It is focused upon one of the subprojects of a previously approved IRB protocol (12681). It focuses upon one aspect of subproject 4 of that proposal. Insulin resistance (IR) is a well-known component of Type 2 diabetes and cardiovascular disease. However, short-term IR is a necessary physiological phenomenon in states such as pregnancy. Maintenance of normal glucose levels during IR is dependent upon the ability of the insulin-secreting beta cells to increase their output in order to overcome the resistance to insulin action that occurs in IR. This proposal will study the physiology of the compensatory increase in insulin secretion in IR. The signal to the beta cells to increase insulin secretion during IR is not well defined; though thought to be glucose, there is reason to suspect that glucose is only part of the mechanism, if at all. The possibility of alternative signaling, beta cell compensatory factors (BCCF) will be studied using the physiological phenomenon of spontaneous IR of pregnancy and comparing it to an experimental model of short-term, drug-induced IR. In addition, preliminary studies of proteomics will be used to initiate identification of potentially new BCCF molecules. Understanding signals for beta cell compensation to IR may lead to new therapeutic possibilities for the prevention or treatment of Type 2 diabetes.