Abstract
Insulin resistance is a characteristic finding in hyperglycaemia and type 2 diabetes. SIRT1 is a NAD+ dependent deacetylase that plays a central role in glucose homeostasis and energy metabolism. SIRT1 activators, including plant polyphenols such as resveratrol, improve insulin sensitivity in skeletal muscle tissue. We hypothesised that the novel plant-derived compounds, strigolactone and pinosylvin, beneficially enhance SIRT1 function, insulin signalling, glucose uptake, and mitochondrial biogenesis in skeletal muscle cells. Rat L6 skeletal muscle myotubes were treated with strigolactone analogue GR24 and pinosylvin. Resveratrol was included in experiments as a reference compound. We measured the effects of these compounds on SIRT1 function, insulin signalling, glucose uptake, mitochondrial biogenesis and gene expression profiles. Strigolactone GR24 upregulated and activated SIRT1 without activating AMPK, enhanced insulin signalling, glucose uptake, GLUT4 translocation and mitochondrial biogenesis. Pinosylvin activated SIRT1 in vitro and stimulated glucose uptake through the activation of AMPK. The regulation of SIRT1 by strigolactone GR24 and the activation of AMPK by pinosylvin may offer novel therapeutic approaches in the treatment of insulin resistance in skeletal muscle.
Highlights
Type 2 diabetes, characterised by impaired insulin secretion and insulin resistance, is an important global health problem[1]
We investigated the effects of strigolactone analogue GR24 and pinosylvin on SIRT1 function, insulin sensitivity, mitochondrial biogenesis and gene expression in differentiated skeletal muscle cells
We hypothesised that the two plant-derived compounds, GR24 and pinosylvin, may have beneficial effects on glucose and energy metabolism and we investigated their effects on SIRT1 function, glucose uptake
Summary
Type 2 diabetes, characterised by impaired insulin secretion and insulin resistance, is an important global health problem[1]. SIRT1 activation mimics calorie restriction[3], and has beneficial effects in age-related diseases, such as cardiovascular, neurodegenerative and metabolic diseases, including type 2 diabetes[4]. SIRT1 activation controls glucose and lipid metabolism in several tissues[5,6,7,8], improves insulin sensitivity[9,10], stimulates mitochondrial biogenesis[11], and decreases obesity-induced inflammation in macrophages[9]. SIRT1 activators, including plant polyphenols such as resveratrol, have beneficial effects on glucose homeostasis and insulin sensitivity in animal models[15]. We hypothesised that strigolactone and pinosylvin have beneficial effects on glucose and energy metabolism, and www.nature.com/scientificreports/. We investigated the effects of strigolactone analogue GR24 and pinosylvin on SIRT1 function, insulin sensitivity, mitochondrial biogenesis and gene expression in differentiated skeletal muscle cells
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