Genetic and pharmacological inhibition of vanin-1 activity in animal models of type 2 diabetes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-04

AUTHORS

Janna A. van Diepen, Patrick A. Jansen, Dov B. Ballak, Anneke Hijmans, Floris P.J.T. Rutjes, Cees J. Tack, Mihai G. Netea, Joost Schalkwijk, Rinke Stienstra

ABSTRACT

Vanins are enzymes that convert pantetheine to pantothenic acid (vitamin B5). Insights into the function of vanins have evolved lately, indicating vanin-1 to play a role in inflammation, oxidative stress and cell migration. Moreover, vanin-1 has recently gained attention as a novel modulator of hepatic glucose and lipid metabolism. In the present study, we investigated the role of vanin-1 in the development of hepatic steatosis and insulin resistance in animal models of obesity and diabetes. In addition, we evaluated the potency of RR6, a novel pharmacological vanin-1 inhibitor, as an anti-diabetic drug. Increased vanin activity was observed in plasma and liver of high fat diet (HFD)-induced obese mice, as well as ZDF-diabetic rats. Ablation of vanin-1 (Vnn1(-/-) mice) mildly improved glucose tolerance and insulin sensitivity in HFD-fed mice, but had no effects on body weight, hepatic steatosis or circulating lipid levels. Oral administration of RR6 for 8 days completely inhibited plasma vanin activity, but did not affect hepatic glucose production, insulin sensitivity or hepatic steatosis in ZDF-diabetes rats. In conclusion, absence of vanin-1 activity improves insulin sensitivity in HFD-fed animals, yet short-term inhibition of vanin activity may have limited value as an anti-diabetic strategy. More... »

PAGES

21906

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep21906

DOI

http://dx.doi.org/10.1038/srep21906

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043270228

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26932716


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