195-OR: The P66Shc Protein Mediates Insulin Resistance in Pancreatic ß Cells Under Lipotoxic Conditions

Insulin, acting in an autocrine manner, promotes β-cell survival and growth and its own biosynthesis and secretion. Prolonged exposure of β-cells to high levels of saturated fatty acids (SFAs) impairs insulin signaling, reducing the ability of insulin to promote its release. The p66Shc protein is an inducer of cellular oxidative stress and apoptosis, and its mRNA levels are increased in pancreatic islets from overweight/obese subjects. Here we evaluated the role of p66Shc in pancreatic β-cell insulin resistance (IR) occurring in obesity and lipotoxic conditions. Insulin effects on its own content and C-peptide secretion were studied in pancreatic islets from overweight/obese (BMI ≥25 kg/m2) compared to lean (BMI