title: 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.
abstract: 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.
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ido
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000375:Aging; D000818:Animals; D002096:C-Peptide / Q000378:metabolism; D048909:Diabetes Complications / Q000235:genetics* / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000378:metabolism; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D025461:Feedback, Physiological; D000071316:Forkhead Box Protein O3 / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000150:complications; D007333:Insulin Resistance; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: D002096:C-Peptide; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D009243:NAD; D055372:AMP-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Adenosine monophosphate-activated protein kinase; C-peptide; Sirtuin 1