Liver is the major site for glycogen storage. Glycogen content can be significantly altered upon disruption of glucose homeostasis in metabolic syndromes, such as diabetes. Glycogen content can be determined by an acid-hydrolysis method (Passonneau and Lauderdale, 1974). Basically, glucose, the hydrolysis product of glycogen, is converted into glucose-6-phosphate (G-6-P) by hexokinase in the presence of ATP. With the supply of NADP, G-6-P is further converted into 6-phosphogluconic acid by G-6-P dehydrogenase (G-6-PDH), while production of NADPH can be measured spectrophotometrically. Our lab has used this method to demonstrate that liver glycogen levels are significantly elevated in diabetic Perk knockout mice (Zhang et al., 2002).