Effect of elevated nutrient availability on intracellular balance redox and insulin resistance in skeletal muscle

Abstract

Insulin resistance is focused on disordered lipid metabolism. This study evaluated the effects of elevated nutrient availability on intracellular balance redox and insulin resistance. The rat soleus muscles were isolated and pre‐incubated in krebs medium during 4h containing glucose 5,6 mM at presence of either palmitate (750 uM) plus insulin (100 μU/mL) or insulin (100 μU/mL). The muscles were also treated with N‐Acetylcysteine (NAC) (1 mM) or electrically submitted to muscle contraction (60 min). The medium was wash‐out and the muscle incubated in krebs ringer containing glucose 5,6 mM at presence of insulin (100 μU/mL) during 60 min. The oxygen consumption; ROS; uptake of 2‐deoxyglucose (2‐DG); NAD+/NADH ratio; mRNA of PGC1α and SIRT1 and glycogen synthesis were evaluated. The O2 consumption and glucose uptake were significantly reduced at presence of palmitate plus insulin (39.9±1U vs 57.1±0.1, p<0.05) and (195±3 vs 100±2%, p<0.05). The glycogen content was also reduced in this conditions (100±1 vs 65±1%, p<0.05). The NAD+/NADH ratio as well as mRNA of PGC1α and SIRT1 were reduced at presence of palmitate plus insulin (p< 0.05). The nitrated protein level at presence of palmitate plus insulin (p< 0.05) was increased (p<0.05). The antioxidant NAC partially improved glucose uptake compared with control (200±2 vs 100±3%, p<0.05). Whereas, muscle contractions increased glucose uptake compared with control (305±5 vs 100±3%, p<0.05). Our results showed that elevated nutrient availability reduce mitochondrial oxygen consumption favoring ROS production and consequently insulin resistance.