Abstract
Sirtuins are energy sensors which mediate effects of calorie restriction-induced lifespan extension. The mammalian sirtuin homolog SIRT1 is a protein deacetylase playing a central role in metabolic homeostasis. SIRT1 is one of the targets of resveratrol, a polyphenol that has been shown to increase lifespan and to protect animal models against high-calorie diet induced obesity and insulin resistance. The beneficial effects of resveratrol mediated by SIRT1 activation can be contributed by different organs. Among them, the liver and pancreatic β-cells have been shown to be responsive to resveratrol in a SIRT1-dependent manner. Downstream of SIRT1, transcription factors being activated are tissue-specific, in turn inducing expression of metabolic genes in an apparent paradoxical way. In this review, we discuss specificities of SIRT1 effects in the liver versus pancreatic β-cells, ultimately converging towards metabolic homeostasis at the organism level.
Highlights
Δhigh‐calorie diet induced obesity and insulin resistance
Resveratrol, a natural polyphenol found for instance in red grapes and wine, is well recognized as a SIRT1 activator [6]
Detailed mechanisms mediating resveratrol effects remain unclear since this molecule has various molecular targets; e.g. SIRT1, AMPactivated protein kinase (AMPK), or antioxidants properties
Summary
Δhigh‐calorie diet induced obesity and insulin resistance. The beneficial effects of resveratrol mediated by SIRT1 activation can be contributed by different organs. AGING, April 2011, Vol.3 No.4 positively regulates glucose-stimulated insulin secretion in pancreatic ß-cells [12, 13]. The SIRT1 activator resveratrol potentiates glucose-stimulated insulin secretion, both acutely and secondary to chronic treatment. Chronic treatment of insulin-secreting cells with resveratrol results in elevated glycolytic flux, increased glucose oxidation and oxygen consumption, thereby producing more ATP upon glucose stimulation [14].
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