GIP and hyperinsulinemic hypoglycemia, familial, 4: Factors contributing to β-cell failure include: aging and genetic predisposition, incretin resistance/deficiency (e.g., impaired glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP] signaling), lipotoxicity (FFA-induced β-cell apoptosis) and glucotoxicity (chronic hyperglycemia-induced oxidative stress), insulin resistance-induced β-cell stress, islet amyloid deposition (excessive islet amyloid polypeptide [IAPP] aggregation), reactive oxygen species (ROS)-mediated damage and proinflammatory signaling (8).