beta-Arrestins as Important Regulators of Glucose and Energy Homeostasis

beta-Arrestin-1 and -2 (also known as arrestin-2 and -3, respectively) are ubiquitously expressed cytoplasmic proteins that dampen signaling through G protein-coupled receptors. However, beta-arrestins can also act as signaling molecules in their own right. To investigate the potential metabolic roles of the two beta-arrestins in modulating glucose and energy homeostasis, recent studies analyzed mutant mice that lacked or overexpressed beta-arrestin-1 and/or -2 in distinct, metabolically important cell types. Metabolic analysis of these mutant mice clearly demonstrated that both beta-arrestins play key roles in regulating the function of most of these cell types, resulting in striking changes in whole-body glucose and/or energy homeostasis. These studies also revealed that beta-arrestin-1 and -2, though structurally closely related, clearly differ in their metabolic roles under physiological and patho-physiological conditions. These new findings should guide the development of novel drugs for the treatment of various metabolic disorders, including type 2 diabetes and obesity.