The role of exercise and hypoxia on glucose transport and regulation

Abstract

Muscle glucose transport activity increases with an acute bout of exercise, a process that is accomplished by the translocation of glucose transporters to the plasma membrane. This process remains intact in the skeletal muscle of individuals with insulin resistance and type 2 diabetes mellitus (T2DM). Exercise training is, therefore, an important cornerstone in the management of individuals with T2DM. However, the acute systemic glucose responses to carbohydrate ingestion are often augmented during the early recovery period from exercise, despite increased glucose uptake into skeletal muscle. Accordingly, the first aim of this review is to summarize the knowledge associated with insulin action and glucose uptake in skeletal muscle and apply these to explain the disparate responses between systemic and localized glucose responses post-exercise. Herein, the importance of muscle glycogen depletion and the key glucoregulatory hormones will be discussed. Glucose uptake can also be stimulated independently by hypoxia; therefore, hypoxic training presents as an emerging method for enhancing the effects of exercise on glucose regulation. Thus, the second aim of this review is to discuss the potential for systemic hypoxia to enhance the effects of exercise on glucose regulation.

Keywords: Exercise; Glucose; Glucose metabolism; Hypoxia; Insulin resistance.

Fig. 1

Proposed pathways mediating translocation of GLUT-4 to the cell membrane of skeletal myocyte in response to insulin and exercise/contraction with and without additional hypoxic stimulus. Upon insulin binding, the activated insulin receptor initiates downstream metabolic signalling that recruits diverse substrates, which ultimately leads to the translocation and fusion of the glucose transporter storage vesicle to the cell membrane and insertion of GLUT-4. Exercise and muscle contraction stimulate GLUT-4 translocation and glucose uptake through a distinct mechanism independent of insulin. This mechanism involves changes in cellular energy status, intracellular Ca²⁺ concentration, reactive oxygen species (ROS) and nitric oxide (NO). Hypoxia activates GLUT-4 translocation via similar or overlapping pathways to that of contraction-mediated glucose uptake. The (+) indicates the proposed potentiation of the hypoxia stimulus

Fig. 2

Glucoregulatory effects of key hormones controlling plasma glucose concentration. Effect of insulin on the liver, adipose tissue and skeletal muscle pathways are demonstrated, along with counter-regulatory effects of epinephrine and norepinephrine, growth hormone and glucagon