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The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes

(2018) DIABETOLOGIA. 61(9). p.2054-2065
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Abstract
Aims/hypothesis: 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. hepatocytes, recombinant WISP1 impaired insulin action by inhibiting phosphorylation of insulin receptor. Akt and its substrates glycogen synthase kinase 3 beta, FOXO1 and p70S6 kinase, and inhibiting insulin-stimulated glycogen synthesis and suppression of gluconeogenic genes. Methods: 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. Results: 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 WISPI 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 Conclusions/interpretation: 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.
Keywords
Adipokine, Akt, Insulin action, Insulin resistance, Type 2 diabetes, Visceral adipose tissue, WISP1, HUMAN SKELETAL-MUSCLE, ADIPOSE-TISSUE, METABOLIC DYSFUNCTION, CROSS-TALK, WNT, OBESITY, INFLAMMATION, SENSITIVITY, ACTIVATION, PROTEINS

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MLA
Hörbelt, Tina, et al. “The Novel Adipokine WISP1 Associates with Insulin Resistance and Impairs Insulin Action in Human Myotubes and Mouse Hepatocytes.” DIABETOLOGIA, vol. 61, no. 9, 2018, pp. 2054–65, doi:10.1007/s00125-018-4636-9.
APA
Hörbelt, T., Tacke, C., Markova, M., Herzfeld de Wiza, D., Van de Velde, F., Bekaert, M., … Ouwens, M. (2018). The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes. DIABETOLOGIA, 61(9), 2054–2065. https://doi.org/10.1007/s00125-018-4636-9
Chicago author-date
Hörbelt, Tina, Christopher Tacke, Mariya Markova, Daniella Herzfeld de Wiza, Frederique Van de Velde, Marlies Bekaert, Yves Van Nieuwenhove, et al. 2018. “The Novel Adipokine WISP1 Associates with Insulin Resistance and Impairs Insulin Action in Human Myotubes and Mouse Hepatocytes.” DIABETOLOGIA 61 (9): 2054–65. https://doi.org/10.1007/s00125-018-4636-9.
Chicago author-date (all authors)
Hörbelt, Tina, 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 FH Pfeiffer, Annette Schürmann, Bruno Lapauw, Natalia Rudovich, Olga Pivovarova, and Margriet Ouwens. 2018. “The Novel Adipokine WISP1 Associates with Insulin Resistance and Impairs Insulin Action in Human Myotubes and Mouse Hepatocytes.” DIABETOLOGIA 61 (9): 2054–2065. doi:10.1007/s00125-018-4636-9.
Vancouver
1.
Hörbelt T, Tacke C, Markova M, Herzfeld de Wiza D, Van de Velde F, Bekaert M, et al. The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes. DIABETOLOGIA. 2018;61(9):2054–65.
IEEE
[1]
T. Hörbelt et al., “The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes,” DIABETOLOGIA, vol. 61, no. 9, pp. 2054–2065, 2018.
@article{8605859,
  abstract     = {{Aims/hypothesis: 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. hepatocytes, recombinant WISP1 impaired insulin action by inhibiting phosphorylation of insulin receptor. Akt and its substrates glycogen synthase kinase 3 beta, FOXO1 and p70S6 kinase, and inhibiting insulin-stimulated glycogen synthesis and suppression of gluconeogenic genes. 
Methods: 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. 
Results: 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 WISPI 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 
Conclusions/interpretation: 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.}},
  author       = {{Hörbelt, Tina and Tacke, Christopher and Markova, Mariya and Herzfeld de Wiza, Daniella and Van de Velde, Frederique and Bekaert, Marlies and Van Nieuwenhove, Yves and Hornemann, Silke and Rödiger, Maria and Seebeck, Nicole and Friedl, Elisabeth and Jonas, Wenke and Thoresen, G Hege and Kuss, Oliver and Rosenthal, Anke and Lange, Volker and Pfeiffer, Andreas FH and Schürmann, Annette and Lapauw, Bruno and Rudovich, Natalia and Pivovarova, Olga and Ouwens, Margriet}},
  issn         = {{0012-186X}},
  journal      = {{DIABETOLOGIA}},
  keywords     = {{Adipokine,Akt,Insulin action,Insulin resistance,Type 2 diabetes,Visceral adipose tissue,WISP1,HUMAN SKELETAL-MUSCLE,ADIPOSE-TISSUE,METABOLIC DYSFUNCTION,CROSS-TALK,WNT,OBESITY,INFLAMMATION,SENSITIVITY,ACTIVATION,PROTEINS}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{2054--2065}},
  title        = {{The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes}},
  url          = {{http://dx.doi.org/10.1007/s00125-018-4636-9}},
  volume       = {{61}},
  year         = {{2018}},
}

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