BETA CELL COMPENSATORY FACTORS IN INSULIN RESISTANCE

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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 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，最好的例子是怀孕等状态，其中第三个三个月的IR是严重的。 当存在对胰岛素作用的抗性时，正常葡萄糖水平的维持取决于分泌胰岛素的β细胞增加其输出的能力，以便通过分泌足够的胰岛素来克服这种抗性。 这项建议将研究胰岛素抵抗中胰岛素分泌代偿性增加的生理学。 导致IR期间胰岛素分泌增加的β细胞信号尚未明确。 虽然传统上认为是葡萄糖，但有理由怀疑葡萄糖只是信号的一部分，如果有的话。 替代信号的可能性，我们称之为β细胞补偿因子（BCCF）的建议，将主要使用短期的实验模型，药物诱导的IR进行研究。在支持这个模型，我们还将研究几个自发的IR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.