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Sirt3 AND metformin

Yen-Chun Lai, Diana M Tabima, John J Dube, Kara S Hughan, Rebecca R Vanderpool, Dmitry A Goncharov, Claudette M St Croix, Adolfo Garcia-Ocaña, Elena A Goncharova, Stevan P Tofovic, Ana L Mora, Mark T Gladwin
BACKGROUND: Pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly recognized clinical complication of metabolic syndrome. No adequate animal model of PH-HFpEF is available, and no effective therapies have been identified to date. A recent study suggested that dietary nitrate improves insulin resistance in endothelial nitric oxide synthase null mice, and multiple studies have reported that both nitrate and its active metabolite, nitrite, have therapeutic activity in preclinical models of pulmonary hypertension...
February 23, 2016: Circulation
Yuping Song, Jingli Shi, Ying Wu, Chong Han, Junjie Zou, Yongquan Shi, Zhimin Liu
BACKGROUND: SIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin. However, the molecular mechanisms underlying this process are unclear. METHODS: The effects of SIRT3 on the regulation of oxidative stress and insulin resistance in skeletal muscle were evaluated in vitro. Differentiated L6 skeletal muscle cells were treated with 750 µmol/L palmitic acid to induce insulin resistance...
2014: Chinese Medical Journal
Marcin Buler, Sanna-Mari Aatsinki, Valerio Izzi, Johanna Uusimaa, Jukka Hakkola
The sirtuins (SIRTs; SIRT1-7) are a family of NAD(+)-dependent enzymes that dynamically regulate cellular physiology. Apart from SIRT1, the functions and regulatory mechanisms of the SIRTs are poorly defined. We explored regulation of the SIRT family by 2 energy metabolism-controlling factors: peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and AMP-activated protein kinase (AMPK). Overexpression of PGC-1α in mouse primary hepatocytes increased SIRT5 mRNA expression 4-fold and also the protein in a peroxisome proliferator-activated receptor α (PPARα)- and estrogen-related receptor α (ERRα)-dependent manner...
July 2014: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Marcin Buler, Sanna-Mari Aatsinki, Valerio Izzi, Jukka Hakkola
Metformin inhibits ATP production in mitochondria and this may be involved in the anti-hyperglycemic effects of the drug. Sirtuin 3 (SIRT3) is a mitochondrial protein deacetylase that regulates the function of the electron transport chain and maintains basal ATP yield. We hypothesized that metformin treatment could diminish mitochondrial ATP production through downregulation of SIRT3 expression. Glucagon and cAMP induced SIRT3 mRNA in mouse primary hepatocytes. Metformin prevented SIRT3 induction by glucagon...
2012: PloS One
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