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Sirtuins: novel targets for metabolic disease

Curr Opin Investig Drugs. 2008 Apr;9(4):371-8.

Abstract

Sirtuins represent a novel family of enzymes that are collectively well situated to help regulate nutrient sensing and utilization, metabolic rate and ultimately metabolic disease. Activation of one of these enzymes, SIRT1, leads to enhanced activity of multiple proteins, including peroxisome-proliferator activated receptor coactivator-1alpha (PGC-1alpha), which helps to mediate some of the in vitro and in vivo effects of sirtuins. As such, enhanced SIRT1 activity decreases glucose levels, improves insulin sensitivity, increases mitochondrial number and function, decreases adiposity, improves exercise tolerance and potentially lowers body weight. SRT-501 is a proprietary formulation of resveratrol with improved bioavailability. As such, SRT-501 represents the first in a novel class of SIRT1 activators that has proven to be safe and well-tolerated in humans. Clinical trials in type 2 diabetic patients are currently underway.

Publication types

  • Review

MeSH terms

  • Base Sequence
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / enzymology
  • Energy Metabolism / drug effects
  • Enzyme Activators / chemistry
  • Enzyme Activators / pharmacology
  • Enzyme Activators / therapeutic use*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Metabolic Diseases / drug therapy*
  • Metabolic Diseases / enzymology
  • Molecular Sequence Data
  • Molecular Structure
  • Obesity / drug therapy
  • Obesity / enzymology
  • Resveratrol
  • Sirtuin 1
  • Sirtuins / agonists*
  • Sirtuins / genetics
  • Sirtuins / metabolism
  • Stilbenes / chemistry
  • Stilbenes / pharmacology
  • Stilbenes / therapeutic use*

Substances

  • Enzyme Activators
  • Enzyme Inhibitors
  • Stilbenes
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins
  • Resveratrol