Specific suppression of insulin sensitivity in growth hormone receptor gene-disrupted (GHR-KO) mice attenuates phenotypic features of slow aging.
Specific suppression of insulin sensitivity in growth hormone receptor gene-disrupted (GHR-KO) mice attenuates phenotypic features of slow aging.
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DOI：
10.1111/acel.12262
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发表时间：
2014-12
期刊：
影响因子：
7.8
通讯作者：
Bartke A
中科院分区：
文献类型：
--
作者：
Arum O;Boparai RK;Saleh JK;Wang F;Dirks AL;Turner JG;Kopchick JJ;Liu JL;Khardori RK;Bartke A
除了延长寿命外，缓慢衰老的生长激素受体/结合蛋白基因破坏（敲除）（GHR-KO）小鼠还具有低胰岛素血症，对胰岛素的作用高度敏感。有人提出，这种胰岛素敏感性对他们的长寿和增加健康寿命很重要。我们测试了GHR-KO小鼠的这种胰岛素敏感性是否是其延缓衰老所必需的，通过用转基因改变消除这种敏感性，该转基因改变通过在大鼠胰岛素启动子1（RIP：：IGF-1）下表达Igf-1来改善胰腺β细胞的发育和分泌功能。RIP：：IGF-1转基因增加了GHR-KO小鼠的循环胰岛素含量，从而使其胰岛素敏感性完全正常化，而不影响任何非β细胞细胞类型的增殖。这些小鼠的多种（非存活）长寿相关的生理和内分泌特征（即有益的血糖调节控制、代谢改变和记忆能力保留）部分或完全正常化，从而支持胰岛素敏感性对GHR-KO小鼠衰老减缓的因果作用。我们的结论是，延迟发病和/或衰老的步伐放缓，可以通过神经调节。
In addition to their extended lifespans, slow-aging growth hormone receptor/binding protein gene-disrupted (knockout) (GHR-KO) mice are hypoinsulinemic and highly sensitive to the action of insulin. It has been proposed that this insulin sensitivity is important for their longevity and increased healthspan. We tested whether this insulin sensitivity of the GHR-KO mouse is necessary for its retarded aging by abrogating that sensitivity with a transgenic alteration that improves development and secretory function of pancreatic β-cells by expressing Igf-1 under the rat insulin promoter 1 (RIP::IGF-1). The RIP::IGF-1 transgene increased circulating insulin content in GHR-KO mice, and thusly fully normalized their insulin sensitivity, without affecting the proliferation of any non-β-cell cell types. Multiple (nonsurvivorship) longevity-associated physiological and endocrinological characteristics of these mice (namely beneficial blood glucose regulatory control, altered metabolism, and preservation of memory capabilities) were partially or completely normalized, thus supporting the causal role of insulin sensitivity for the decelerated senescence of GHR-KO mice. We conclude that a delayed onset and/or decreased pace of aging can be hormonally regulated.
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影响因子：
15.9
作者：
ACHESON, K;JEQUIER, E;WAHREN, J
通讯作者：
WAHREN, J
影响因子：
3.7
作者：
Boparai RK;Arum O;Khardori R;Bartke A
通讯作者：
Bartke A
影响因子：
15.9
作者：
ACHESON, KJ;RAVUSSIN, E;JEQUIER, E
通讯作者：
JEQUIER, E
影响因子：
--
作者：
Arum, Oge;Saleh, Jamal K.;Bartke, Andrzej
通讯作者：
Bartke, Andrzej
DOI：
10.1093/gerona/glp175
发表时间：
2010-01-01
影响因子：
5.1
作者：
Berryman, Darlene E.;List, Edward O.;Kopchick, John J.
通讯作者：
Kopchick, John J.