Decreased plasma neuregulin 4 levels are associated with peripheral neuropathy in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study

Yan, Pingping; Xu, Yong; Zhang, Zhihong; Gao, Chenlin; Zhu, Jianhua; Li, Hua; Wan, Qin

doi:10.1016/j.cyto.2018.10.007

Cited by 30 publications

(47 citation statements)

References 45 publications

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“…Work performed by Cai et al revealed that plasma Nrg4 levels were negatively related to FBG in subjects with obesity. Consistently, a recent study conducted on Chinese patients by Yan and colleagues showed that the plasma Nrg4 concentration was markedly lower in nT2DM patients with no diabetic peripheral neuropathy (DPN) than in healthy controls and was even further reduced in nT2DM patients with DPN. Moreover, Nrg4 levels were remarkably reduced in individuals with abnormal DPN screening results.…”

Section: Discussionsupporting

confidence: 58%

“…Adipose tissue is recognized as a highly active metabolic organ that is the primary storage site for excess energy, but it also serves as an endocrine organ, secreting a number of biologically active compounds, known as adipocytokines or adipokines, involved in the modulation of metabolic homeostasis . Neuregulin 4 (Nrg4) is one of these adipokines and is related to obesity, dyslipidaemia, insulin resistance (IR), inflammation, and oxidative stress (OS) in mouse models and in humans …”

Section: Introductionmentioning

confidence: 99%

“…Neuregulins (Nrg1‐4) are ligands for the receptor tyrosine kinases of the ErbB/HER family, which is involved in the regulation of diverse biological processes . Nrg1 and Nrg2 bind to both ErbB3 (HER3) and ErbB4 (HER4), whereas Nrg3 and Nrg4 preferentially bind to ErbB4 . ErbB4 contains multiple properties compared with the other ErbB family members, which makes it a potentially unique and selective target in terms of signalling as well as in having an important role in human disease .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A systematic review of the association of neuregulin 4, a brown fat–enriched secreted factor, with obesity and related metabolic disturbances

et al. 2019

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Neuregulin 4 (Nrg4), a novel brown fat-enriched hormone, plays a key role in the modulation of glucose and lipid metabolism and energy balance. Recent data have demonstrated that the expression of Nrg4 is substantially down-regulated in mouse and human obesity, making its regulatory aspect intriguing. Because of the close relationship between Nrg4, obesity, and associated metabolic diseases, this systematic review aimed to assess the association of Nrg4 with obesity and related metabolic disturbances, emphasizing its possible mechanisms of action in these disorders. We searched PubMed/Medline, ScienceDirect, Scopus, EMBASE, ProQuest, and Google Scholar up until June 2019. The evidence reviewed here indicates that Nrg4 may contribute to the prevention of obesity and related metabolic complications by elevating brown adipose tissue activity, increasing the expression of thermogenic markers, decreasing the expression of lipogenic/ adipogenic genes, exacerbating white adipose tissue browning, increasing the number of brite/beige adipocytes, promoting hepatic fat oxidation and ketogenesis, inducing neurite outgrowth, enhancing blood vessels in adipose tissue, increasing the circulatory levels of healthy adipokines, and improving glucose homeostasis.Thus, Nrg4 appears to be a novel therapeutic strategy for the treatment of obesity and associated metabolic complications. However, prospective cohort studies are warranted to confirm these outcomes.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A systematic review of the association of neuregulin 4, a brown fat–enriched secreted factor, with obesity and related metabolic disturbances

et al. 2019

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“…In an 11-year cohort study, the inflammatory biomarkers C-reactive protein and pro-adrenomedullin were independently associated with cardiovascular events and all-cause mortality in type 2 DM patients [26]. Additionally, compared with controls, elevated serum levels of tumor necrotic factor-α and decreased neuregulin-4 (a novel adipokine) were found in diabetic patients and correlated with the severity of diabetic peripheral neuropathy [27,28]. Yeniel et al assessed atherosclerosis indicators and blood perfusion in the bladder necks in women with OAB.…”

Section: Diabetes and Bladder Inflammationmentioning

confidence: 99%

The Pharmacological Mechanism of Diabetes Mellitus-Associated Overactive Bladder and Its Treatment with Botulinum Toxin A

Wang

Jiang

Kuo

2020

Toxins

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Diabetes mellitus (DM) is an independent risk factor for overactive bladder (OAB). The pathophysiology of DM-associated OAB is multifactorial and time-dependent. Diabetic bladder dysfunction is highly associated with diabetic complications, mainly including diabetic neuropathy and atherosclerosis. Chronic systemic inflammation and bladder urothelial inflammation may contribute to the onset of OAB. Intravesical botulinum toxin A (BoNT-A) injection has proved to be a successful treatment for idiopathic and neurogenic OAB. BoNT-A can inhibit the efferent pathways of the bladder as well as the chronic inflammation and hypersensitivity via the afferent pathways. We conducted a review of the published literature in Pubmed using a combination of two keywords, namely “botulinum toxin A” (BoNT-A) and “overactive bladder”, with or without the additional keywords “detrusor overactivity”, “diabetes mellitus”, “inflammation”, and “urodynamic study”. We also reviewed the experience of our research teams, who have published several studies of the association between DM and OAB. Since limited data support the effectiveness and safety of BoNT-A for treating patients with DM-associated OAB, a comprehensive evaluation of diabetic complications and urodynamic study is needed before treatment. In the future, it is imperative to explore the clinical characteristics and inflammatory biomarkers of diabetes as determining predictors of the treatment efficacy.

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“…Among these proteins is neuregulin 4 (Nrg4), a novel adipocytokine, which is mainly secreted by brown adipose tissue. This adipocytokine is a member of the epidermal growth factor (EGF) family of extracellular ligands, which specifically activates EGF receptor ErbB4 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) to improve systemic energy metabolism 3 and preserve glucose homeostasis [3][4][5] .…”

mentioning

confidence: 99%

Clinical significance of serum concentrations of neuregulin-4, in acute coronary syndrome

Rahimzadeh

Farshidi

Naderi

et al. 2020

Sci Rep

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Acute coronary syndrome (ACS) is closely associated with an increased risk of death. Nrg4, a novel adipocytokine, has negative correlations with indicators of metabolic syndrome. Here, we investigated whether circulating Nrg4 associates with the prevalence of ACS. In this case-control study, a total of 257 subjects (144 patients with ACS and 56 patients diagnosed with stable angina pectoris (SAP)) compared to 57 healthy controls. Serum Nrg4 and hs-CRP concentrations were determined by ELISA. The associations of circulating Nrg4 with other clinical parameters were also analyzed. Serum levels of Nrg4 were lower in patients compared to the control subjects (0.7 ± 0.53 ng/mL versus 1.1 ± 0.9 ng/mL, p = 0.018). There was a significant association between higher Nrg4 level and lower risk of ACS (OR = 0.15; 95%CI = 0.02-0.9; P = 0.046), but not with SAP. This association was independent of potential confounders including traditional cardiovascular risk factors. The distribution of patients with no, 1, 2 and 3 vessel stenosis was significantly different in Nrg4 quartiles. Patients in the lower quartile of Nrg4 were more likely to experience 3 vessel diseases. Serum levels of Nrg4 correlated negatively with HDL-cholesterol in ACS patients. Decreased serum levels of Nrg4 might be an independent risk factor for ACS.

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Decreased plasma neuregulin 4 levels are associated with peripheral neuropathy in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study

Cited by 30 publications

References 45 publications

A systematic review of the association of neuregulin 4, a brown fat–enriched secreted factor, with obesity and related metabolic disturbances

A systematic review of the association of neuregulin 4, a brown fat–enriched secreted factor, with obesity and related metabolic disturbances

The Pharmacological Mechanism of Diabetes Mellitus-Associated Overactive Bladder and Its Treatment with Botulinum Toxin A

Clinical significance of serum concentrations of neuregulin-4, in acute coronary syndrome

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