Journal of Diabetes and its Complications
Exenatide treatment increases serum irisin levels in patients with obesity and newly diagnosed type 2 diabetes
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.
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Study design and participants
Fifty-four obese patients with newly diagnosed with type 2 diabetes (T2D group) were consecutively enrolled from March 2013 to December 2013 at the Department of Endocrinology in Beijing Chao-yang Hospital Affiliated with Capital Medical University (Consultation, 2004). An oral glucose tolerance test (OGTT) was performed at screening. All patients had been diagnosed with type 2 diabetes within the previous 3 months according to the 2013 American Diabetes Association diagnostic criteria (American
Baseline patient characteristics
Baseline characteristics of the T2D and control groups are summarized in Table 1. Age, sex, and BMI were similar between groups, whereas increased TG, FBG, HbA1c, and HOMA-IR levels and decreased HOMA-β and HDL-C levels were observed in the T2D group compared to the control group (all P < 0.01). TC, LDL-C, and FINS levels were not different between the two groups. Importantly, serum irisin levels were significantly lower in the T2D group than those in the control group (38.06 [29.29–53.79] vs.
Discussion
In the present study, obese patients with newly diagnosed type 2 diabetes (T2D group) had significantly lower serum irisin levels than obese subjects with normal glucose tolerance (control group). In addition, serum irisin levels in the T2D group were negatively associated with BMI, FBG, and HbA1c levels. In accordance with the improvements in metabolic parameters, exenatide treatment markedly increased serum irisin levels. The increase in serum irisin level after exenatide treatment was
Conclusion
In conclusion, obese patients with newly diagnosed type 2 diabetes had significantly lower irisin levels. The GLP-1 receptor agonist exenatide significantly increased serum irisin levels in the T2D group, and this increase was significantly correlated with decreases in FBG and HbA1c. These results suggest that the upregulation of irisin might be a novel mechanism for the beneficial effects of exenatide in patients with type 2 diabetes.
Funding
This work was supported by grants from the Major National Basic Research Program of P. R. China (No. 2011CB503904), the Chinese National Natural Science Foundation (No. 81270369, 81070244, 30770873), and the Beijing Natural Science Foundation (No. 7142060) to Guang Wang. This work was further supported by the foundation of the Beijing Key Laboratory of Metabolic Disturbance Related Cardiovascular Disease and Beijing Municipal Administration of Hospitals' Youth Programme (QML20150308) to Jia Liu.
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Disclosure: The authors declare that they have no conflicts of interest concerning this article.
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These authors contributed equally to this work.