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

The primary physiological role of insulin is in glucose homeostasis. This i s accomplished through the inhibition of gluconeogenesis in the liver and t he stimulation of glucose uptake into insulin-sensitive tissues, such as ad ipose 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 intra cellular compartment to the plasma membrane, which results in increased glu cose uptake. Defects in the ability of insulin to regulate this key metabol ic event can lead to insulin resistance and non-insulin-dependent type 2 di abetes mellitus (T2DM). To design effective treatments for diabetes, there have been major efforts to understand the insulin-regulate mechanisms that govern glucose uptake. These have involved defining the components of the i nsulin signaling network and identifying the molecular machinery that is us ed to translocate GLUT4.