Can low blood glucose extend health

低血糖可以延长健康吗

基本信息

  • 批准号:
    9324104
  • 负责人:
  • 金额:
    $ 23.46万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-05-01 至 2019-04-30
  • 项目状态:
    已结题

项目摘要

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.
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。 几种延长健康和延迟衰老的模型,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, 尚不清楚低血糖是否对他们的健康和寿命延长很重要。的 一个潜在的价值,以了解血糖和衰老之间的关系是一个转基因 小鼠品系,命名为Inshex,具有健康表型,但具有永久性低血糖,25-50% 低于正常小鼠。这种小鼠最初是为了研究胰腺β细胞而开发的小鼠, 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症,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, 正常大小和肥沃。血糖在500日龄时降低。该项目的首要目标是 以确认血糖永久保持在低水平,并且降低血糖可以延长寿命。 将在30只雄性Inshex和30只非转基因同窝仔的队列中确定寿命, 不受干扰地跟踪以确定小鼠变得濒死并需要安乐死时的年龄。一 兽医病理学家将评估发病原因。在它们的一生中, 每日观察,每月称重。在Inshex和对照小鼠的单独队列中, 将每隔3个月采集一次样本,以测量血糖、HbA 1c、血浆游离脂肪酸 和尿白蛋白与肌酸酐的比率。将在5、10和20月龄处死各组小鼠。 在处死前一天,将小鼠置于代谢室中,通过测定呼吸商, 间接测热法和同时测量步行活动。与其他小鼠模型不同, 低葡萄糖初始结果表明Inshex小鼠具有正常的呼吸商。后 在代谢室中,将动物麻醉用于身体组成的DEXA扫描测量, 用于获得大量血液样本以测量与衰老调节有关的代谢激素 (胰岛素、IGF 1或生长激素)。衰老是人们肾功能丧失的主要原因。一 初步分析表明,在400-500天的Inshex肾中肾小球瘢痕形成较少。的有益 Inshex低葡萄糖对肾脏结构和功能的影响将通过检查肾脏 在5、10和20个月处死对照和Inshex小鼠的组织学,并通过比较年龄 相关的白蛋白渗漏到尿液中。这些研究将证明是否低血 葡萄糖可以延长肾脏功能和小鼠寿命。

项目成果

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PAUL N EPSTEIN的其他文献

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{{ truncateString('PAUL N EPSTEIN', 18)}}的其他基金

Can low blood glucose extend health
低血糖可以延长健康吗
  • 批准号:
    9035960
  • 财政年份:
    2016
  • 资助金额:
    $ 23.46万
  • 项目类别:
Podocytes and oxidative stress in diabetic kidney
糖尿病肾的足细胞和氧化应激
  • 批准号:
    8013681
  • 财政年份:
    2010
  • 资助金额:
    $ 23.46万
  • 项目类别:
Prolonged Diabetic Damage to Cardiac Mitochondria
长期糖尿病对心脏线粒体的损​​害
  • 批准号:
    8004397
  • 财政年份:
    2009
  • 资助金额:
    $ 23.46万
  • 项目类别:
Prolonged Diabetic Damage to Cardiac Mitochondria
长期糖尿病对心脏线粒体的损​​害
  • 批准号:
    7027938
  • 财政年份:
    2006
  • 资助金额:
    $ 23.46万
  • 项目类别:
Prolonged Diabetic Damage to Cardiac Mitochondria
长期糖尿病对心脏线粒体的损​​害
  • 批准号:
    7564106
  • 财政年份:
    2006
  • 资助金额:
    $ 23.46万
  • 项目类别:
Prolonged Diabetic Damage to Cardiac Mitochondria
长期糖尿病对心脏线粒体的损​​害
  • 批准号:
    7334221
  • 财政年份:
    2006
  • 资助金额:
    $ 23.46万
  • 项目类别:
Prolonged Diabetic Damage to Cardiac Mitochondria
长期糖尿病对心脏线粒体的损​​害
  • 批准号:
    7166828
  • 财政年份:
    2006
  • 资助金额:
    $ 23.46万
  • 项目类别:
Podocytes and oxidative stress in diabetic kidney
糖尿病肾的足细胞和氧化应激
  • 批准号:
    6956678
  • 财政年份:
    2005
  • 资助金额:
    $ 23.46万
  • 项目类别:
Podocytes and oxidative stress in diabetic kidney
糖尿病肾的足细胞和氧化应激
  • 批准号:
    7467297
  • 财政年份:
    2005
  • 资助金额:
    $ 23.46万
  • 项目类别:
Podocytes and oxidative stress in diabetic kidney
糖尿病肾的足细胞和氧化应激
  • 批准号:
    7262452
  • 财政年份:
    2005
  • 资助金额:
    $ 23.46万
  • 项目类别:
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