Organizing glucose disposal - Emerging roles of the glycogen targeting subunits of protein phosphatase-1

Glucose is stored in mammalian tissues in the form of glycogen. Glycogen le vels are markedly reduced in liver or muscle cells of patients with insulin -resistant or insulin-deficient forms of diabetes, suggesting that impaired glycogen synthesis may contribute to development of hyperglycemia. Recentl y, interest in this area has been further stimulated by new insights into t he spatial organization of metabolic enzymes within cells and the importanc e of such organization in regulation of glycogen metabolism. It is now clea r that a four-member family of glycogen targeting subunits of protein phosp hatase-1 (PP1) plays a major role in coordinating these events. These prote ins target PP1 to the glycogen particle and also bind differentially to gly cogen synthase, glycogen phosphorylase, and phosphorylase kinase, thereby s erving as molecular scaffolds. Moreover, the various glycogen-targeting sub units have distinct tissue expression patterns and can influence regulation of glycogen metabolism in response to glycogenic and glycogenolytic signal s. The purpose of this article is to summarize new insights into the struct ure, function, regulation, and metabolic effects of the glycogen-targeting subunits of PP1 and to evaluate the possibility that these molecules could serve as therapeutic targets for lowering of blood glucose in diabetes.