Diabetic complications within the context of aging: Nicotinamide adenine dinucleotide redox, insulin C-peptide, sirtuin 1-liver kinase B1-adenosine monophosphate-activated protein kinase positive feedback and forkhead box O3.
Diabetic complications within the context of aging: Nicotinamide adenine dinucleotide redox, insulin C-peptide, sirtuin 1-liver kinase B1-adenosine monophosphate-activated protein kinase positive feedback and forkhead box O3.
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尼古丁酰胺腺苷二核苷酸氧化还原，胰岛素C肽，SIRTUIN 1肝激酶B1-腺苷单磷酸激活的蛋白激酶阳性反馈和叉子盒O3。
DOI：
10.1111/jdi.12485
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发表时间：
2016-07
影响因子：
3.2
通讯作者：
Ido Y
中科院分区：
文献类型：
--
作者：
Ido Y
最近的营养控制衰老的研究表明，还原型烟酰胺腺嘌呤二核苷酸的胞质增加和烟酰胺腺嘌呤二核苷酸代谢的减少在控制长寿基因产物sirtuin 1（SIRT 1），腺苷酸激活蛋白激酶（AMPK）和叉头盒O3（FOXO 3）中起着核心作用。高营养条件，如糖尿病环境，通过包括多元醇途径在内的级联增加细胞溶质烟酰胺腺嘌呤二核苷酸的还原与氧化形式的比率。这种氧化还原变化与胰岛素抵抗和糖尿病并发症的发生有关，并且可能被胰岛素C肽抵消。我和其他人的研究表明，SIRT 1-肝激酶B1-AMPK级联通过烟酰胺腺嘌呤二核苷酸合成产生正反馈，帮助细胞科普代谢应激。SIRT 1和AMPK可以上调肝激酶B1和FOXO 3，这是帮助住宅干细胞科普氧化应激的关键因素。FOXO 3直接改变转录起始位点周围的表观遗传学，维持干细胞的健康。“糖尿病记忆”可能是由高营养条件引起的表观遗传变化的结果，这会扰乱住宅干细胞的静止状态并损害组织修复。这可以通过激活FOXO 3恢复SIRT 1-AMPK正反馈来预防。
Recent research in nutritional control of aging suggests that cytosolic increases in the reduced form of nicotinamide adenine dinucleotide and decreasing nicotinamide adenine dinucleotide metabolism plays a central role in controlling the longevity gene products sirtuin 1 (SIRT1), adenosine monophosphate‐activated protein kinase (AMPK) and forkhead box O3 (FOXO3). High nutrition conditions, such as the diabetic milieu, increase the ratio of reduced to oxidized forms of cytosolic nicotinamide adenine dinucleotide through cascades including the polyol pathway. This redox change is associated with insulin resistance and the development of diabetic complications, and might be counteracted by insulin C‐peptide. My research and others' suggest that the SIRT1–liver kinase B1–AMPK cascade creates positive feedback through nicotinamide adenine dinucleotide synthesis to help cells cope with metabolic stress. SIRT1 and AMPK can upregulate liver kinase B1 and FOXO3, key factors that help residential stem cells cope with oxidative stress. FOXO3 directly changes epigenetics around transcription start sites, maintaining the health of stem cells. ‘Diabetic memory’ is likely a result of epigenetic changes caused by high nutritional conditions, which disturb the quiescent state of residential stem cells and impair tissue repair. This could be prevented by restoring SIRT1–AMPK positive feedback through activating FOXO3.