Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes

By J. Milne, P. Lambert, S. Schenk, David P. Carney, Jesse J. Smith, D. Gagne, Lei Jin, O. Boss, R. Perni, C. Vu and 18 more. Nature, 2007

1,756 citations recorded by the source corpus.

Subfields: Epidemiology, Geriatrics and Gerontology, Physiology

View Paper: https://www.semanticscholar.org/paper/746c2d7e1bca081ef77565803d3af997a57e9dad

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Citations in the corpus

SIRT1 and other sirtuins in Metabolism (2013, background): “In addition, SIRT1 activators like resveratrol [44] and newer sirtuin activating compounds (STACs) [45], exert effects that are similar to those of CR as revealed by measures of whole animal physiology [46] or by transcriptional profiling [47].”
Mitochondrial Energetics and Therapeutics (2010, positive): “The success of this approach has already been reported for several age-related diseases, including type 2 diabetes (274).”
Hepatocyte-specific Deletion of SIRT1 Alters Fatty Acid Metabolism and Results in Hepatic Steatosis and Inflammation (2009, background): “For example, activation of SIRT1 by the polyphenol resveratrol and several synthetic pharmacologic activators has been shown to protect against high-fat induced obesity and metabolic derangements (Baur et al., 2006; Lagouge et al., 2006; Milne et al., 2007).”
Plant polyphenols as dietary antioxidants in human health and disease (2009, background): “Many mechanisms have been proposed to explain the anti-diabetic action of this stilbene, modulation of SIRT1 is one of them which improves whole-body glucose homeostasis and insulin sensitivity in diabetic rats.(50,68) It is reported that in cultured LLC-PK1 cells, high glucose induced cytotoxicity ”
Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. (2008, background): “A new generation of selective synthetic SIRT1 activators structurally unrelated to resveratrol and with improved potency, efficacy, and specificity have recently been developed (Milne et al., 2007).”
Transcriptional control of mitochondrial biogenesis and function. (2009, background): “F or p er so na l u se o nl y. ANRV369-PH71-09 ARI 5 January 2009 14:42 Sirtuin 1 (SIRT1): NAD+-dependent protein deacetylase homologous to the yeast silent information regulator (Sir2) and implicated in caloric restriction and aging pathways Histone deacetylase (HDAC): a family of enzymes that deac”
The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. (2010, background): “Compounds such as SRT1720, which more specifically target SIRT1 and have the similar effect on T2DM at lower doses, might facilitate clinical development (102, 207).”
Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases (2012, positive): “Because the metabolic effects of SRT1720 are nearly identical to those of resveratrol (Milne et al., 2007; Feige et al., 2008), it is tempting to speculate that these compounds, or at least SRT1720, act via pathways similar to those of resveratrol.”
The Histone Deacetylase SIRT6 Regulates Glucose Homeostasis via Hif1α (2010, neutral): “In this context, whereas SIRT1 activators have been shown to protect against metabolic diseases such as type II diabetes, as published (Baur et al., 2006; Lagouge et al., 2006; Milne et al., 2007), in the case of SIRT6, inhibition rather than activation might prove beneficial to lower blood glucose ”
Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders (2010, neutral): “In one study, the shortening of lifespan by the high-fat diet was reversed (305).”
SIRTUIN 1 AND SIRTUIN 3: PHYSIOLOGICAL MODULATORS OF METABOLISM (2012, background): “These molecules, 1,000 times more potent than resveratrol but structurally distinct (220), were shown to act through the same enzymatic mechanism, i.”