Can low blood glucose extend health

世界人口老龄化使延长健康成为比以往任何时候都更加重要的优先事项。 几种延长健康和延缓衰老的模型，如热量限制和小鼠模型 侏儒症表现为低血糖。然而，这些模型具有复杂的生理学，而且它是 不知道低血糖是否对延长他们的健康和寿命很重要。的 转基因技术对了解血糖与衰老关系的潜在价值 小鼠品系，命名为Inshex，具有健康的表型但永久低血糖，25%-50% 低于正常小鼠。小鼠最初是用来研究胰腺β细胞和 糖尿病。Inshex转基因导致胰腺β细胞胰岛素分泌反应左移 但最终的表型是低血糖，血清胰岛素水平几乎正常。这 该提案将使用Inshex小鼠来测试血糖是否会影响衰老。Inshex小鼠是健康的， 体型正常，有生育能力。血糖在500天龄时降低。这个项目的第一个目标是 以确认血糖长期保持在低水平，并且降低血糖可以延长寿命。 寿命将在30只雄性Inshex和30只非转基因产仔的队列中确定，这将是 不受干扰地跟踪以确定小鼠死亡和需要安乐死的年龄。一个 兽医病理学家将对发病原因进行评估。在它们的一生中，老鼠将会是 每天观察，每月称重。在Inshex和对照小鼠的不同队列中，血液和尿液 每隔3个月采集样本，测量血糖、糖化血红蛋白、血浆游离脂肪酸 尿白蛋白/肌酐比值。5个月、10个月和20个月大的小鼠将被处死。 处死前一天，将小鼠放入代谢室测定呼吸商。 间接量热法，同时测量活动能力。与其他鼠标模型不同的是 低血糖的初步结果表明，Inshex小鼠的呼吸商正常。后 代谢室，动物将被麻醉进行DEXA扫描测量身体成分和 获取大量血液样本以测量与衰老调节有关的代谢荷尔蒙 (胰岛素、IGF1或生长激素)。衰老是人类肾功能丧失的主要原因。一个 初步分析表明，400-500天的Inshex肾脏肾小球疤痕较少。受益者 Inshex低糖对肾脏结构和功能的影响将通过肾脏检查得到证实 对照组和Inshex小鼠在5、10和20个月时处死并比较日龄 相关的白蛋白渗入尿液。这些研究将证明低血压症 葡萄糖可延长小鼠的肾脏功能和寿命。

Aging of the world population has made prolongation of health a more important priority than ever. Several models of extended health and delayed aging such as caloric restriction and mouse models of dwarfism demonstrate low blood glucose. However, these models have complex physiology and it is not known whether low blood glucose is important to their prolonged health and extended lifespan. Of potential value to understanding the relationship between blood glucose and aging is a transgenic mouse line, designated Inshex, with a healthy phenotype but permanently low blood glucose, 25-50% lower than normal mice. The mouse was originally developed mice to study pancreatic β-cells and diabetes. The Inshex transgene produced a left shift in the pancreatic β-cell insulin secretion response to glucose but the final phenotype is hypoglycemia with almost normal serum insulin levels. This proposal will use Inshex mice to test if blood glucose influences aging. Inshex mice are healthy, of normal size and fertile. Blood glucose is reduced at 500 days of age. The first goals of this project are to confirm that blood glucose stays low permanently and that reduced blood glucose extends longevity. Lifespan will be determined in cohorts of 30 male Inshex and 30 non-transgenic littermates that will be followed undisturbed to determine the age when mice become moribund and require euthanasia. A veterinary pathologist will assess the cause of morbidity. Over the course of their lives mice will be observed daily and weighed monthly. In separate cohorts of Inshex and control mice, blood and urine samples will be obtained at 3 month intervals to measure blood glucose, HbA1c, plasma free fatty acids and urine albumin to creatinine ratio. Groups of mice will be sacrificed at 5, 10 and 20 months of age. The day before sacrifice mice will be placed in metabolic chambers to determine respiratory quotient by indirect calorimetry and simultaneously measure ambulatory activity. Unlike other mouse models with low glucose initial results indicate that Inshex mice have a normal respiratory quotient. After the metabolic chamber, animals will be anesthetized for DEXA scan measurement of body composition and for obtaining a large blood sample to measure metabolic hormones implicated in modulation of aging (insulin, IGF1 or growth hormone). Aging is the leading cause for loss of renal function in people. A preliminary analysis indicated less glomerular scarring in 400-500 day Inshex kidneys. The beneficial effect of Inshex low glucose on kidney structure and function will be confirmed by examining renal histology of control and Inshex mice sacrificed at 5, 10 and 20 months and by comparing age associated leakage of albumin into the urine. These studies will demonstrate whether low blood glucose extends function of the kidney and lifespan of the mouse.