Glycogen storage disease type I Glycogen storage disease type I Glycogen storage disease type I (GSD I) or von Gierke disease, is the most common of the glycogen storage diseases. This genetic disease results from deficiency of the enzyme glucose-6-phosphatase, and has an incidence in the American population of approximately 1 in 50,000 to 100,000 births. The deficiency impairs the ability of the liver to produce free glucose from glycogen and from gluconeogenesis. Since these are the two principal metabolic mechanisms by which the liver supplies glucose to the rest of the body during periods of fasting, it causes severe hypoglycemia and results in increased
Glycogen synthase protein phosphatase 1 (PP1), which activates glycogen synthase via dephosphorylation. PP1 is targeted to the glycogen pellet by four targeting subunits, G, G, PTG and R6. These regulatory enzymes are regulated by insulin and glucagon signaling pathways. Mutations in the "GYS1" gene are associated with glycogen storage disease type 0. In humans, defects in the tight control of glucose uptake and utilization are also associated with diabetes and hyperglycemia. Patients with type 2 diabetes normally exhibit low glycogen storage levels because of impairments in insulin-stimulated glycogen synthesis and suppression of glycogenolysis. Insulin stimulates glycogen synthase by inhibiting glycogen synthase kinases