| Title |
The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes
|
|---|---|
| Published in |
Diabetologia, May 2018
|
| DOI | 10.1007/s00125-018-4636-9 |
| Pubmed ID | |
| Authors |
Tina Hörbelt, Christopher Tacke, Mariya Markova, Daniella Herzfeld de Wiza, Frederique Van de Velde, Marlies Bekaert, Yves Van Nieuwenhove, Silke Hornemann, Maria Rödiger, Nicole Seebeck, Elisabeth Friedl, Wenke Jonas, G. Hege Thoresen, Oliver Kuss, Anke Rosenthal, Volker Lange, Andreas F. H. Pfeiffer, Annette Schürmann, Bruno Lapauw, Natalia Rudovich, Olga Pivovarova, D. Margriet Ouwens |
| Abstract |
Wingless-type (Wnt) inducible signalling pathway protein-1 (WISP1) has been recently identified as a proinflammatory adipokine. We examined whether WISP1 expression and circulating levels are altered in type 2 diabetes and whether WISP1 affects insulin signalling in muscle cells and hepatocytes. Serum and visceral adipose tissue (VAT) biopsies, for analysis of circulating WISP1 levels by ELISA and WISP1 mRNA expression by real-time quantitative RT-PCR, were collected from normal-weight men (control group, n = 33) and obese men with (n = 46) and without type 2 diabetes (n = 56) undergoing surgery. Following incubation of primary human skeletal muscle cells (hSkMCs) and murine AML12 hepatocytes with WISP1 and insulin, insulin signalling was analysed by western blotting. The effect of WISP1 on insulin-stimulated glycogen synthesis and gluconeogenesis was investigated in hSkMCs and murine hepatocytes, respectively. Circulating WISP1 levels were higher in obese men (independent of diabetes status) than in normal-weight men (mean [95% CI]: 70.8 [55.2, 86.4] ng/l vs 42.6 [28.5, 56.6] ng/l, respectively; p < 0.05). VAT WISP1 expression was 1.9-fold higher in obese men vs normal-weight men (p < 0.05). Circulating WISP1 levels were positively associated with blood glucose in the OGTT and circulating haem oxygenase-1 and negatively associated with adiponectin levels. In hSkMCs and AML12 hepatocytes, recombinant WISP1 impaired insulin action by inhibiting phosphorylation of insulin receptor, Akt and its substrates glycogen synthase kinase 3β, FOXO1 and p70S6 kinase, and inhibiting insulin-stimulated glycogen synthesis and suppression of gluconeogenic genes. Circulating WISP1 levels and WISP1 expression in VAT are increased in obesity independent of glycaemic status. Furthermore, WISP1 impaired insulin signalling in muscle and liver cells. |
X Demographics
The data shown below were collected from the profiles of 10 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 30% |
| United Kingdom | 2 | 20% |
| Spain | 1 | 10% |
| Unknown | 4 | 40% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 60% |
| Scientists | 3 | 30% |
| Practitioners (doctors, other healthcare professionals) | 1 | 10% |
Mendeley readers
The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 42 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 8 | 19% |
| Student > Master | 7 | 17% |
| Student > Bachelor | 5 | 12% |
| Student > Doctoral Student | 4 | 10% |
| Student > Ph. D. Student | 4 | 10% |
| Other | 3 | 7% |
| Unknown | 11 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 12 | 29% |
| Biochemistry, Genetics and Molecular Biology | 8 | 19% |
| Agricultural and Biological Sciences | 3 | 7% |
| Nursing and Health Professions | 2 | 5% |
| Psychology | 2 | 5% |
| Other | 4 | 10% |
| Unknown | 11 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 86. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 June 2018.
All research outputs
#422,316
of 23,065,445 outputs
Outputs from Diabetologia
#230
of 5,092 outputs
Outputs of similar age
#10,552
of 325,590 outputs
Outputs of similar age from Diabetologia
#5
of 56 outputs
Altmetric has tracked 23,065,445 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,092 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 22.7. This one has done particularly well, scoring higher than 95% of its peers.
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We're also able to compare this research output to 56 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 91% of its contemporaries.