USE OF AN IN VIVO MODEL SYSTEM TO INVESTIGATE NIDDM

使用体内模型系统研究 NIDDM

• 批准号: 3767774
• 负责人: J EGAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3767774
• 关键词: aging; disease /disorder model; dosage; gastrointestinal hormones; hormone regulation /control mechanism; insulin; laboratory rat; noninsulin dependent diabetes mellitus; pancreatic islet function; secretion

Age is an independent risk factor for NIDDM. Age is also associated with a decline in insulin secretion. Using 6-cells from Wistar rats from the colony of aged rats at the GRC, we showed that insulin release in response to glucose decreases with age of the donor. This is a result of fewer beta cells releasing insulin as well as less insulin released per cell. We found that mRNA for insulin is preferentially diminished in islets, with glucokinase and glucagon messages unaffected. Therefore, it appears that throughout the lifespan of the rat, insulin message is decreasing. Islets compensate for this by increasing size. But, eventually this compensation becomes inadequate. Therefore, one can envision when a stress is put on the system so more insulin is required, diabetes could result. We are exploring what factors lead to this diminution of insulin message and the possibility that we can prevent or reverse it.

年龄是 NIDDM 的独立危险因素。 年龄也与 胰岛素分泌下降。 使用 Wistar 大鼠的 6 细胞 在 GRC 的老年大鼠群体中，我们发现胰岛素释放响应 葡萄糖随着捐赠者年龄的增长而降低。这是测试版较少的结果 细胞释放胰岛素以及每个细胞释放的胰岛素较少。我们 发现胰岛素的 mRNA 在胰岛中优先减少， 葡萄糖激酶和胰高血糖素信息不受影响。因此，看来 在大鼠的整个生命周期中，胰岛素信息不断减少。胰岛 通过增加尺寸来补偿这一点。但最终这个补偿 变得不充分。因此，人们可以想象当压力施加在 系统需要更多的胰岛素，可能会导致糖尿病。我们是 探索哪些因素导致胰岛素信息的减少以及 我们可以预防或扭转它的可能性。