| Autor: |
van Diepen JA; Department of Internal Medicine, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands., Jansen PA; Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, 6525 GA Nijmegen, The Netherlands., Ballak DB; Department of Internal Medicine, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands., Hijmans A; Department of Internal Medicine, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands., Rutjes FP; Institute for Molecules and Materials, Radboud University Nijmegen, 6525 GA Nijmegen, The Netherlands., Tack CJ; Department of Internal Medicine, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands., Netea MG; Department of Internal Medicine, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands., Schalkwijk J; Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, 6525 GA Nijmegen, The Netherlands., Stienstra R; Department of Internal Medicine, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands.; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6703 HA, Wageningen, the Netherlands. |
| Abstrakt: |
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. |
