Circulating serum irisin levels in obesity and type 2 diabetes mellitus

Shoukry, A; Shalaby, Sally M.; Bdeer, Shereen El-Arabi; Mahmoud, Amira A.; Mouśa, M. A.; Khalifa, Ashraf

doi:10.1002/iub.1511

Cited by 94 publications

(100 citation statements)

References 48 publications

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“…Of particular interest in this context is irisin, a newly identified adipomyokine derived from fibronectin type III domain containing 5 (FNDC5), which has gained attention for its potential in the prevention and treatment of obesity and T2DM [6,7]. In this regard, the circulating levels of irisin were found to be altered in obese individuals and diabetic patients [8]; these levels were considered to be one biomarker for the prediction of the development of diabetes and mortality risk of cardiovascular diseases [9,10]. We and others have demonstrated that, in an overnutrition state, irisin can restore metabolic homeostasis, thereby alleviating insulin resistance and protecting cell function as well as survival in hepatic tissues [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Irisin Ameliorates Glucolipotoxicity-Associated β-Cell Dysfunction and Apoptosis via AMPK Signaling and Anti-Inflammatory Actions

Zhang¹,

Xie²,

Leung³

2018

Cell Physiol Biochem

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Background/Aims: Islet metabolic disorder and inflammation contribute to the pathogenesis and progression of type 2 diabetes mellitus (T2DM). Irisin is a recently identified adipomyokine with protective effects on metabolic homeostasis and inflammation-suppressing effects in hepatic and vascular cells. The present study examined the effects of irisin on lipid metabolism and inflammation in β cells under glucolipotoxic conditions. Methods: Rat INS-1E β cells and islets isolated from C57BL/6 mice were incubated in glucolipotoxic conditions with or without irisin. Intracellular lipid contents and lipogenic gene expression were determined by enzymatic colorimetric assays and real-time PCR, respectively. Inflammatory status was evidenced by Western blot analysis for the phosphorylation of nuclear factor-κB (NF-κB) p65 and real-time PCR analysis for the expression of pro-inflammatory genes. Results: Irisin reversed glucolipotoxicity-induced intracellular non-esterified fatty acid (NEFA) and triglyceride accumulation, suppressed associated elevations in lipogenic gene expression, and phosphorylated acetyl-CoA-carboxylase (ACC) in INS-1E cells. These demonstrated effects were dependent on irisin-activated adenosine monophosphate-activated protein kinase (AMPK). Meanwhile, AMPK signaling mediated the protective effects of irisin on INS-1E cell insulin secretory ability and survival as well. Additionally, irisin inhibited phosphorylation of NF-κB p65 while decreasing the expression of pro-inflammatory genes in INS-1E cells under glucolipotoxic conditions. Moreover, irisin also improved insulin secretion, inhibited apoptosis, and restored β-cell function-related gene expression in isolated mouse islets under glucolipotoxic conditions. Conclusion: Irisin attenuated excessive lipogenesis in INS-1E cells under glucolipotoxic state through activation of AMPK. Irisin also suppressed overnutrition-induced inflammation in INS-1E cells. Our findings implicate irisin as a promising therapeutic target for the treatment of islet lipid metabolic disorder and islet inflammation in T2DM.

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Section: Introductionmentioning

confidence: 99%

Irisin Ameliorates Glucolipotoxicity-Associated β-Cell Dysfunction and Apoptosis via AMPK Signaling and Anti-Inflammatory Actions

Zhang¹,

Xie²,

Leung³

2018

Cell Physiol Biochem

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“…Irisin also mediates the beneficial metabolic effects of exercise and has a potentially favorable effect on obesity and diabetes. Previous studies have reported that the serum level of irisin is positively related to the body mass index (4,5) and serum fatty acid profile (5)(6)(7)(8). However, the relationship between irisin and glucose metabolism is quite complicated, and results concerning the correlation between irisin and fast insulin have been controversial (9)(10)(11).…”

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confidence: 99%

Irisin promotes proliferation but inhibits differentiation in osteoclast precursor cells

et al. 2018

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The receptor activator of NF-κB ligand-induced osteoclast differentiation has a critical role in the process of bone metabolism. Overactivation of osteoclastogenesis may result in a series of diseases. Irisin, a novel myokine, which was first reported in 2012, has been proposed to mediate the beneficial metabolic effects of exercise. Studies have demonstrated that irisin targets osteoblasts by promoting osteoblast proliferation and differentiation; however, the underlying mechanism regarding the effect of irisin on osteoclasts remains elusive. Using 2 types of osteoclast precursor cells, RAW264.7 cells and mouse bone marrow monocytes, we showed that irisin promoted osteoclast precursor cell proliferation but inhibited osteoclast differentiation. Irisin down-regulated the expression of osteoclast differentiation marker genes, including receptor activators of NF-κB, nuclear factor of activated T cells, cytoplasmic 1, cathepsin K, and tartrate-resistant acid phosphatase (TRAP), as well as decreasing the number of TRAP-positive multinucleated cells and hydroxyapatite resorption pits. Furthermore, we showed that irisin suppressed the NF-κB signaling pathway, but activated the p38 and JNK signaling pathways. In the presence of an inhibitor of p38 and JNK, irisin-induced promotion of RAW264.7 cell proliferation was attenuated. However, irisin-induced inhibition of osteoclast differentiation was not affected by either the p38 or JNK signaling pathway. Our study suggested the direct effect of irisin on osteoclastogenesis and revealed the mechanism responsible for the therapeutic potential of irisin in bone metabolism disease.-Ma, Y., Qiao, X., Zeng, R., Cheng, R., Zhang, J., Luo, Y., Nie, Y., Hu, Y., Yang, Z., Zhang, J., Liu, L., Xu, W., Xu, C. C., Xu, L. Irisin promotes proliferation but inhibits differentiation in osteoclast precursor cells.

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“…Irisin is a novel hormone (myokine) secreted by cardiac and skeletal myocytes in response to exercise that may regulate metabolism and limit weight gain, although its precise role is controversial (106, 107). Circulating levels of irisin are reported to be reduced or increased in obese subjects, but reduced in type 2 diabetic patients (106, 108, 109). Lower levels of irisin are associated with endothelial dysfunction (109, 110).…”

Section: Potential Targets or Approachesmentioning

confidence: 99%

Targeting Obesity and Diabetes to Treat Heart Failure with Preserved Ejection Fraction

et al. 2017

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Heart failure with preserved ejection fraction (HFpEF) is a major unmet medical need that is characterized by the presence of multiple cardiovascular and non-cardiovascular comorbidities. Foremost among these comorbidities are obesity and diabetes, which are not only risk factors for the development of HFpEF, but worsen symptoms and outcome. Coronary microvascular inflammation with endothelial dysfunction is a common denominator among HFpEF, obesity, and diabetes that likely explains at least in part the etiology of HFpEF and its synergistic relationship with obesity and diabetes. Thus, pharmacological strategies to supplement nitric oxide and subsequent cyclic guanosine monophosphate (cGMP)—protein kinase G (PKG) signaling may have therapeutic promise. Other potential approaches include exercise and lifestyle modifications, as well as targeting endothelial cell mineralocorticoid receptors, non-coding RNAs, sodium glucose transporter 2 inhibitors, and enhancers of natriuretic peptide protective NO-independent cGMP-initiated and alternative signaling, such as LCZ696 and phosphodiesterase-9 inhibitors. Additionally, understanding the role of adipokines in HFpEF may lead to new treatments. Identifying novel drug targets based on the shared underlying microvascular disease process may improve the quality of life and lifespan of those afflicted with both HFpEF and obesity or diabetes, or even prevent its occurrence.

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Circulating serum irisin levels in obesity and type 2 diabetes mellitus

Cited by 94 publications

References 48 publications

Irisin Ameliorates Glucolipotoxicity-Associated β-Cell Dysfunction and Apoptosis via AMPK Signaling and Anti-Inflammatory Actions

Irisin Ameliorates Glucolipotoxicity-Associated β-Cell Dysfunction and Apoptosis via AMPK Signaling and Anti-Inflammatory Actions

Irisin promotes proliferation but inhibits differentiation in osteoclast precursor cells

Targeting Obesity and Diabetes to Treat Heart Failure with Preserved Ejection Fraction

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