Naomi Nishio, Tadao Hasegawa
Ken-ichi Isobe, Murine model of obesity-induced type II diabetes by GADD34 (PPP1R15A) and other phosphatase 1 regulatory subunits deficiency.(2016)SDRP Journal Of Infectious Diseases Treatment & Therapy 1(1)
Obesity-derived metabolic syndrome is one of the most important medical problems in the world. Recently, we have developed murine model of age-dependent obesity and metabolic syndrome including Type II diabetes by using GADD34-deficient mice. GADD34 belongs one of phosphatase 1 regulatory subunits named PPP1R15A. Deficiency of glycogen-targeting regulatory subunits (G subunits) has been shown to develop metabolic diseases. Glycogen synthesis is mainly controlled by glycogen synthase (GS) and glycogen phosphorylase (GP). G subunits work to up-regulate glycogen synthesis by activating GS and suppressing GP. Seven G subunits (PPP1R3A to PPP1R3G) works to increase glycogen. PPP1R3A deficient mice became obese by age and showed insulin resistance. Because GADD34 binds several target proteins and PP1c catalytic subunit, GADD34 (PPP1R15A) has several functions in different stimulations by dephosphorylating target proteins. With age GADD34-deficient mice become obese, developing fatty liver followed by liver cirrhosis, hepatocellular carcinoma, and insulin resistance.