BETA CELL COMPENSATORY FACTORS IN INSULIN RESISTANCE

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。 胰岛素抵抗(IR)是2型糖尿病和心血管疾病等疾病的一个众所周知的组成部分。然而，短期IR也是一种生理现象，最好的例证是怀孕等状态，在这些状态下，第三个月的IR是严重的。当存在胰岛素抵抗时，维持正常血糖水平依赖于分泌胰岛素的β细胞增加其产量的能力，以便通过分泌足够的胰岛素来克服这种抵抗。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。 IR期间导致胰岛素分泌增加的β细胞信号还没有很好的定义。虽然传统上被认为是葡萄糖，但有理由怀疑葡萄糖只是信号的一部分，如果真的有的话。对于这一建议，我们称之为β细胞代偿因子(BCCF)的替代信号的可能性将主要使用短期药物诱导IR的实验模型进行研究。为了支持这一模型，我们还将研究IR的几个自发模型。

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. Insulin resistance (IR) is a well-known component of disorders such as Type 2 diabetes and cardiovascular disease. However, short-term IR is also a physiological phenomenon, best exemplified by states such as pregnancy, where IR by the 3rd trimester is severe. Maintenance of normal glucose levels when there is resistance to insulin action is dependent upon the ability of the insulin-secreting beta cells to increase their output in order to overcome this resistance by secreting enough insulin. This proposal will study the physiology of the compensatory increase in insulin secretion in IR. The signal to the beta cell that results in an increase of insulin secretion during IR is not well defined. Though traditionally thought to be glucose, there is reason to suspect that glucose is only part of the signal, if at all. The possibility of alternative signaling, which we have called beta cell compensatory factors (BCCF) for this proposal, will be studied primarily using an experimental model of short-term, drug-induced IR. In support of this model we will also study several spontaneous models of IR.