Relative efficacies of insulin and poly (lactic-co-glycolic) acid encapsulated nano-insulin in modulating certain significant biomarkers in arsenic intoxicated L6 cells

The present study evaluates relative efficacies of insulin and PLGA-loaded-nano-insulin (NIn) in combating arsenic-induced impairment of glucose uptake, insulin resistance and mitochondrial dysfunction in L6 skeletal muscle cells. L6 cells were treated with 0.5 mM sodium arsenite for 30 min and then the cells were further treated with either 100 nM insulin (standardized dose) or either of the two doses, 50 nM and 100 nM of nano-insulin. Various biomarkers like pyruvate-kinase and glucokinase, ATP/ADP ratio, mitochondrial membrane potential, cytosolic release of mitochondrial cytochrome c, cell membrane potential and calcium-ion level were studied and analyzed to ascertain the status of mitochondrial functioning in all experimental and control sets of L6 cells. The size, morphology and zeta potential of formulated NIn were determined by using dynamic light scattering, scanning electronic and atomic-force microscopies. Expression of signalling cascades like GLUT4, IRS1, IRS2, UCP2, PI3, and p38 was critically analyzed. Overall results suggested that both insulin and NIn improved mitochondrial functioning in arsenite-intoxicated L6 cells, NIn showing better effects at a much lower dose (at nearly 10-fold decreased dose) than that produced by insulin. Nano-insulin being non-toxic and effective at a much lesser dose, therefore, has potential for therapeutic use in the management of arsenic induced diabetes.