Adenosine, Adenosine Receptors and Their Role in Glucose Homeostasis and Lipid Metabolism

Abstract

Adenosine is an endogenous metabolite that is released from all tissues and cells including liver, pancreas, muscle and fat, particularly under stress, intense exercise, or during cell damage. The role of adenosine in glucose homeostasis has been attributed to its ability to regulate, through its membrane receptors, processes such as insulin secretion, glucose release and clearance, glycogenolysis, and glycogenesis. Additionally, adenosine and its multiple receptors have been connected to lipid metabolism by augmenting insulin-mediated inhibition of lipolysis, and the subsequent increase in free fatty acids and glycerol levels. Furthermore, adenosine was reported to control liver cholesterol synthesis, consequently affecting plasma levels of cholesterol and triglycerides, and the amount of fat tissue. Alterations in the balance of glucose and lipid homeostasis have implications in both cardiovascular disease and diabetes. The ability of different adenosine receptors to activate and inhibit the same signaling cascades has made it challenging to study the influence of adenosine, adenosine analogs and their receptors in health and disease. This review focuses on the role and significance of different adenosine receptors in mediating the effect of adenosine on glucose and lipid homeostasis.

Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia

“…figure 1a,b), although the hypoxic decrease in CO 2 production in AMP-treated naked mole rats was significantly less than that observed in saline-treated animals (figure 1b). This difference may have been due to a secondary effect of AMP on the balance between the catabolism of lipids and carbohydrates as fuel substrates in hypoxic naked mole rats, although this requires further investigation [30,31]. These changes were also reversed following 30 min of recovery in normoxia (to 41…”

Exercise partially reverses the inhibitory effect of caffeine on liver gluconeogenesis in type 1 diabetic rats with hypoglycemia

“…These receptors are found in muscle, liver, and adipose tissue, all of them heavily involved in blood glucose homeostasis. In adipose tissue (A1-subtype receptors), caffeine could result in increased lipolysis and a glucose-saving systemic effect (3,19,24,25,27,38); however, by antagonizing adenosine receptors on skeletal muscle (also A1-subtype receptors), caffeine increases glycolysis (27). In addition, adenosine receptors in Exercise and caffeine in diabetic ratsthe liver stimulate gluconeogenesis, glycogenolysis, and glucose release (14,15,18,21,27,36), all of which could be potentially antagonized by caffeine.…”

Exercise and the Regulation of Adipose Tissue Metabolism

“…Adenosine is an endogenous purine nucleoside that inhibits lipolysis by activation of the A1 adenosine receptor (A 1 AR), which decreases adenylyl cyclase activity and inactivates PKA. 43 While adenosine inhibits lipolysis at rest, studies that infused the adenosine receptor antagonist theophylline during exercise reported no change in lipolysis, 44 questioning the importance of adenosine regulation during exercise.…”