Role of clusterin/ApoJ on insulin signalling in response to physical exercise in rodents and humans

Abstract

Insulin is an anabolic hormone with fundamental actions in organs and tissues to maintain body homeostasis. Abnormalities in insulin action to stimulate glucose uptake in skeletal muscle and inhibit hepatic glucose production, are usually found in individuals with insulin resistance and antecedent the development of type 2 diabetes mellitus (DM2). The hypertrophied adipose tissue releases several biomolecules such as hormones and pro-inflammatory cytokines and other factors that are involved in the induction of insulin resistance in obese. In this context, the knowledge in molecular biology with other fields of study have been trying to guide which factors are most important in the prevention and treatment of DM2. Clusterin, or apolipoprotein J (ApoJ) via its membrane receptor (LRP2) acts in the insulin signaling potentiating its effects on peripheral tissues (skeletal muscle, liver and adipose) and also in the hypothalamus. However, the expression of this protein in peripheral tissues and its mechanisms of action are not fully understood. Physical exercise is also able to regulate crucial proteins involved in insulin signaling and promote metabolic improvements in animal and human diabetics. However, its effects in the regulation of clusterin and consequently in glucose homeostasis have not been elucidated so far. Thus, understanding the molecular mechanisms involved in the action of clusterin in insulin signaling in the liver and muscle tissues in the exercise condition becomes essential for discovery of new therapeutic mechanisms, as well as for more effective prescription of physical exercise and safe for individuals affected by obesity and DM2. (AU)