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

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

*Corresponding author for this work

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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.

Original languageEnglish
Article number21906
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2016

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    Van Diepen, J. A., Jansen, P. A., Ballak, D. B., Hijmans, A., Rutjes, F. P. J. T., Tack, C. J., Netea, M. G., Schalkwijk, J., & Stienstra, R. (2016). Genetic and pharmacological inhibition of vanin-1 activity in animal models of type 2 diabetes. Scientific Reports, 6, [21906]. https://doi.org/10.1038/srep21906