AMPK and Beyond: The Signaling Network Controlling RabGAPs and Contraction-Mediated Glucose Uptake in Skeletal Muscle

Abstract

Impaired skeletal muscle glucose uptake is a key feature in the development of insulin resistance and type 2 diabetes. Skeletal muscle glucose uptake can be enhanced by a variety of different stimuli, including insulin and contraction as the most prominent. In contrast to the clearance of glucose from the bloodstream in response to insulin stimulation, exercise-induced glucose uptake into skeletal muscle is unaffected during the progression of insulin resistance, placing physical activity at the center of prevention and treatment of metabolic diseases. The two Rab GTPase-activating proteins (RabGAPs), TBC1D1 and TBC1D4, represent critical nodes at the convergence of insulin- and exercise-stimulated signaling pathways, as phosphorylation of the two closely related signaling factors leads to enhanced translocation of glucose transporter 4 (GLUT4) to the plasma membrane, resulting in increased cellular glucose uptake. However, the full network of intracellular signaling pathways that control exercise-induced glucose uptake and that overlap with the insulin-stimulated pathway upstream of the RabGAPs is not fully understood. In this review, we discuss the current state of knowledge on exercise- and insulin-regulated kinases, hypoxia, nitric oxide (NO) and bioactive lipids that may be involved in the regulation of skeletal muscle glucose uptake.

Selenium supplementation via modulation of selenoproteins ameliorates binge drinking-induced oxidative, energetic, metabolic, and endocrine imbalance in adolescent rats’ skeletal muscle

“…SKM is a tissue that stands out in this context for being the primary site for glucose disposal in response to insulin or exercise; 24 it can also store glucose and serves as the reservoir of major metabolic amino acid, to be used in case of energy requirements. Regrettably, BD during adolescence has recently been linked to impaired SKM protein turnover.…”