Exenatide treatment increases serum irisin levels in patients with obesity and newly diagnosed type 2 diabetes

Abstract

Objective

Irisin is a myokine secreted by skeletal muscle during exercise. Abnormal serum irisin levels are associated with obesity and type 2 diabetes (T2D). This study investigated the changes in serum irisin in the obese patients with newly diagnosed T2D following glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide) treatment.

Methods

Fifty-four obese patients with T2D were treated with exenatide for 12 weeks. The control group included 54 age-, sex-, and body mass index (BMI)-matched subjects with normal glucose tolerance.

Results

Patients with T2D had lower irisin than the control group (38.06 [29.29–53.79] vs. 58.01 [43.07–87.79] ng/mL, P < 0.01]. Serum irisin was negatively associated with BMI (r = − 0.178, P < 0.05), fasting blood glucose (FBG; r = − 0.170, P < 0.05), and glycosylated hemoglobin (HbA1c; r = − 0.189, P < 0.01) in patients with T2D. Exenatide treatment markedly increased serum irisin by 19.28 ng/mL (12.59–25.98) compared to baseline (P < 0.01). Increased irisin was significantly correlated with decreased FBG and HbA1c after exenatide treatment (FBG: r = − 0.35; HbA1c: r = − 0.37; both P < 0.05).

Conclusions

Exenatide treatment significantly increased irisin in patients with T2D. Post-treatment changes in irisin were correlated with decreases in FBG and HbA1c. The upregulation of irisin might be a novel mechanism for the beneficial effects of exenatide in type 2 diabetic patients.

Introduction

Irisin is a newly discovered myokine (Huh et al., 2014). It is secreted in response to exercise, which stimulates expression of the type I membrane protein fibronectin type III domain-containing protein 5 (FNDC5) in skeletal muscle, and then FNDC5 is cleaved and secreted into the circulation as irisin (Bostrom et al., 2012). Animal studies have shown that irisin regulates energy metabolism and mediates some of the beneficial effects of exercise (Huh et al., 2014). Abnormal serum irisin levels have also been associated with multiple metabolic diseases in human (Liu et al., 2013, Polyzos et al., 2014, Yan et al., 2014). Several studies have demonstrated that patients with type 2 diabetes have decreased serum irisin (Choi et al., 2013, Xiang et al., 2014). Moreover, an animal study showed that metformin, a common hypoglycemic agent especially used in patients with obesity (Li, Yang, et al., 2015), increased FNDC5 expression of skeletal muscle cells and blood irisin levels in diabetic db/db mice (Li, Huang, et al., 2015). Furthermore, in women with polycystic ovary syndrome, metformin elevated circulating irisin levels (Li, Yang, et al., 2015).

Glucagon-like peptide-1 (GLP-1) receptor agonists are novel agents approved for treating type 2 diabetes (Liu, Wang, Jia, & Xu, 2015). In addition to reducing insulin resistance and glucagon production, these agents also enhance energy expenditure and reduce body weight, supporting their use in obese patients with type 2 diabetes (Liu et al., 2015). Several large-scale studies have demonstrated that a GLP-1 receptor agonist increases insulin sensitivity and causes more weight loss than does metformin (Liu et al., 2015, Sun et al., 2015). Similar to irisin, GLP-1 receptor agonists increase peroxisome proliferator-activated receptor α (PPARα) expression and AMP-activated protein kinase phosphorylation (Ding et al., 2006, Lee et al., 2012). These similar effects of GLP-1 receptor agonists and irisin suggest a possible association between GLP-1 receptor agonists and irisin. However, to the best of our knowledge, there have been no studies into the relationship between irisin and GLP-1 receptor agonist treatment. As exenatide is a classical GLP-1 receptor agonist widely used in many countries, our study aimed to investigate the change in serum irisin levels in obese patients with newly diagnosed type 2 diabetes following exenatide treatment.