Chapter 14 - Moonlighting GAPDH and Diabetes: Pleiotropic Effects of Perturbations in GAPDH Structure and Function

Abstract

Diabetes presents as a consequence of the hyperglycemic stress resulting from either a deficiency in the synthesis of insulin or an alteration in its basic mechanisms of cell regulation. Although insulin regulates GAPDH gene expression in normal cells, recent studies indicate fundamental roles for moonlighting GAPDH in the cellular mechanisms, which underlie diabetic pathogenesis. These include hyperglycemic perturbations as a consequence of GAPDH enzyme inhibition following its structural modification by oxidative stress-induced poly (ADP-ribose) polymerase 1, a notable role for moonlighting GAPDH in the development of diabetic retinopathy, as well as its distinctive function in diabetes-related apoptosis. As such, these studies indicate the significance of moonlighting GAPDH in the clinical and cellular presentation of this human disease.