Nuclear co‐repressor (NCoR) is required to maintain insulin sensitivity in C₂C₁₂ myotubes

Abstract

Nuclear co-repressor (NCoR) regulates peripheral insulin sensitivity; however, its role in modulating insulin sensitivity in skeletal muscle remains elusive. Present study investigated protein expression and effect of NCoR on insulin sensitivity in murine skeletal muscle cell line C C . Myotubes as compared to myoblasts of C C cells were found to be more sensitive in response to insulin as increase in insulin-stimulated phosphorylation of AKT at serine 473 residue (pAKT ) was significantly higher in myotubes. Incidentally, reduced protein level of NCoR coincided with differentiation of myoblasts into myotubes of C C cells. However, insulin stimulation per se failed to affect protein level of NCoR either in myoblasts or myotubes of C C cells. To assess the role of NCoR on insulin sensitivity, NCoR was transiently knocked down using siRNA in myotubes of C C . In fact, transient silencing of NCoR led to significant reduction in insulin-stimulated pAKT and impaired glucose uptake. This observation is in contrast to published studies where NCoR has been reported to negatively regulate insulin signaling cascade. Furthermore, transient silencing of NCoR failed to improve insulin sensitivity in chronic hyperinsulinemia-induced insulin-resistant model of C C cells. Importantly, inhibition of lysosomal protein degradation pathway using ammonium chloride restored protein level of NCoR but failed to increase glucose uptake in serum-starved C C myotubes. Collectively, data from present study show differential protein level of NCoR under different cell state (myoblast and myotubes) of C C cells and NCoR proves to be vital for maintaining insulin sensitivity in C C myotubes.

Sleeve gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

“…SG animals also had an upregulation in MECOM-regulated pathways, which are associated with increased purine and pyrimidine metabolism, amino acid metabolism, pentose phosphate pathway reliance, and glycolysis (25). Elevations in PPAR␥, SMRT, and NCOR, which all interact to control downstream adipocyte fate and function, glucose handling, insulin sensitivity, mitochondrial oxidative capacity, and thermogenesis, were also found (14,28,29,40,56,65,69,75). Thus as inferred from the calorimetry data, there is upregulation of transcriptional machinery capable of increasing energy production and glucose utilization within the VAT of SG mice.…”

Sleeve Gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

“…Elevations in PPARg, SMRT, and NCOR which all interact to control downstream adipocyte fate and function, glucose handling, insulin sensitivity, mitochondrial oxidative capacity, and thermogenesis, were also found. [43,49] [36,50] [33] [51][52][53]. Thus, as inferred from the calorimetry data, there is upregulation of transcriptional machinery capable of increasing energy production and glucose utilization within the VAT of SG mice.…”