Direct and Indirect Pathways of Hepatic Glycogen Synthesis in Normal and in Insulin Resistant States pp. 149-162
Authors: (John Griffith Jones, Centro de Neurociencias e Biologia Celular, Departamento de Zoologia, Universidade de Coimbra, Portugal)
Abstract: Over a quarter century has passed since the discovery that mammalian liver converts glucose to glycogen via two distinct metabolic routes, subsequently referred to as ―direct‖ and ―indirect‖ pathways of glycogen synthesis. In the wake of this discovery, the growing consensus that the indirect and gluconeogenic pathways of hepatic glucose-6-phosphate production are one and the same has transformed our way of thinking about the regulation of hepatic glucose and glycogen fluxes during fed to fasting transitions and in the setting of insulin resistance and diabetes. This review will provide a historical perspective of direct/indirect pathway studies, a summary of the various tracer methods that have been developed to measure direct/indirect pathway fluxes and application of these methods to define direct/indirect pathway fluxes under physiological and pathophysiological states. The role of the indirect pathway as an attenuator of hepatic glucose output under fed conditions will be described and the implications of disrupting this activity in the context of hepatic insulin resistance will be discussed.