SIRT1 and fatty liver disease: In addition, whereas SIRT1 overexpression protects against both the hepatic steatosis and glucose intolerance induced by high-fat feeding [86, 87], oligonucleotide knockdown of hepatic SIRT1 in a rat model of T2DM has been reported to reduce hyperglycemia by normalizing basal hepatic glucose production and increasing hepatic insulin sensitivity, leading to the suggestion that novel SIRT1 inhibitors targeted at the liver might prove beneficial in the treatment of T2DM [88].