Insulin receptor activation results in an increase in the flux of glucose into glycogen in skeletal muscle. A defect in which of the following proteins involved in glycogen homeostasis would be expected to result in the greatest deficit in insulinmediated glycogenesis in these cells?
A) glucose 6-phosphatase
B) glycogen synthase-phosphorylase kinase
C) glycogen phosphorylase
D) protein phosphatase inhibitor 1 (PPI-1)
E) protein targeting glycogen (PTG)

Question

Quizplus · Accepted Answer

Protein targeting glycogen (PTG) is crucial for the proper localization and activation of enzymes involved in glycogen synthesis. A defect in PTG would significantly impair insulin-mediated glycogenesis by disrupting the assembly and function of the glycogen synthesis machinery.  One of the many effects of insulin on cells is to increase glucose uptake and storage into glycogen. Glucose uptake (eg, in skeletal muscle) is mediated by insulin-induced mobilization of glucose transporters (GLUT4) to the cell surface. The glucose is then incorporated into glycogen because of insulin's effects on glycogen homeostatic enzymes. These effects are an increase in glycogen synthase and a decrease in glycogen phosphorylase activities. Increased glycogen synthesis is affected by activation of phosphate removal from 3 key enzymes via the action of protein phosphatase 1 (PP-1). These key enzymes are phosphorylase, phosphorylase kinase, and glycogen synthase. Dephosphorylation of the first 2 enzymes reduces their activity, while dephosphorylation of the latter increases its activity leading to increased glucose storage. In order for this regulatory process to be carried out quickly and effectively a subunit of PP-1 collects all of the regulated enzymes into a mutisubunit complex. This subunit is called protein targeting glycogen, PTG. Therefore, a defect in PTG function would reduce or eliminate the ability of insulin action to target glycogen homeostasis.

Insulin Receptor Activation Results in an Increase in the Flux