GLUT4 and company: SNAREing roles in insulin-regulated glucose uptake

Abstract

The primary physiological role of insulin is in glucose homeostasis. This is accomplished through the inhibition of gluconeogenesis in the liver and the stimulation of glucose uptake into insulin-sensitive tissues, such as adipose tissue, skeletal muscle and cardiac muscle. The ability of insulin to stimulate glucose uptake relies on a complex signaling cascade that leads to the translocation of glucose transporter protein 4 (GLUT4) from an intracellular compartment to the plasma membrane, which results in increased glucose uptake. Defects in the ability of insulin to regulate this key metabolic event can lead to insulin resistance and non-insulin-dependent type 2 diabetes mellitus (T2DM). To design effective treatments for diabetes, there have been major efforts to understand the insulin-regulated mechanisms that govern glucose uptake. These have involved defining the components of the insulin signaling network and identifying the molecular machinery that is used to translocate GLUT4.