Abstract
Irisin is a myokine that primarily targets adipose tissue, where it increases energy expenditure and contributes to the beneficial effects of exercise through the browning of white adipose tissue. As our knowledge has deepened in recent years, muscle has been found to be a major target organ for irisin as well. Several studies have attempted to characterize the role of irisin in muscle to improve glucose metabolism through mechanisms such as reducing insulin resistance. Although they are very intriguing reports, some contradictory results make it difficult to grasp the whole picture of the action of irisin on muscle. In this review, we attempted to organize the current knowledge of the role of irisin in muscle glucose metabolism. We discussed the direct effects of irisin on glucose metabolism in three types of muscle, that is, skeletal muscle, smooth muscle, and the myocardium. We also describe irisin’s effects on mitochondria and its interactions with other hormones. Furthermore, to consider the relationship between the irisin-induced improvement of glucose metabolism in muscle and systemic disorders of glucose metabolism, we reviewed the results from animal interventional studies and human clinical studies.
Highlights
Insulin resistance and abnormal insulin secretion are thought to be the major mechanisms of type 2 diabetes (T2DM) onset
There is a debate about the fundamental cause of T2DM, in general, insulin resistance is thought to precede its deficiency in the early stages of onset, and hyperglycemia develops when the relative lack of insulin exceeds the threshold
María et al proposed that in individuals with obesity, fibronectin type III domain-containing protein 5 (FNDC5) expression in muscle was significantly decreased in association with T2DM, and FNDC5 expression in muscle was significantly associated with FNDC5 and uncoupling protein 1 (UCP1) expression in visceral adipose tissue [133]
Summary
Insulin resistance and abnormal insulin secretion are thought to be the major mechanisms of type 2 diabetes (T2DM) onset. Gene expression in muscle and serum levels of myokines show unique patterns of change immediately after the start of exercise, suggesting that the exercise-induced release of myokines may play an important role in coordinating metabolism, leading to a beneficial effect on T2DM treatment [10]. Irisin has attracted a great deal of attention as a therapeutic target for metabolic diseases, including obesity, dyslipidemia, T2DM, and arterial hypertension Based on these findings of FNDC5 in metabolic regulation with the exercise-induced nature of irisin, and the possibility that muscle itself can be irisin’s target organ, researchers have started to look at the role of irisin in exercise-induced effects on muscle glucose metabolism [16,21,22]. The aim of this review is to highlight the emerging knowledge about irisin in glucose homeostasis in three types of muscles in vitro and in vivo under metabolic stresses, such as high-lipid/hyperlipidemia, and high-glucose/hyperglycemia
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