TY  - JOUR
AU  - Diepen, J.A. van
AU  - Jansen, P.A.
AU  - Ballak, D.B.
AU  - Hijmans, A.G.
AU  - Rutjes, F.P.J.T.
AU  - Tack, C.J.
AU  - Netea, M.G.
AU  - Schalkwijk, J.
AU  - Stienstra, R.
PY  - 2016
UR  - https://hdl.handle.net/2066/169892
AB  - 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.
TI  - Genetic and pharmacological inhibition of vanin-1 activity in animal models of type 2 diabetes
SN  - 2045-2322
JF  - Scientific Reports
VL  - vol. 6
DO  - https://doi.org/10.1038/srep21906
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/169892/169892.pdf?sequence=1
ER  -