Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes.
Bottom Line: The emergence of bone as an endocrine regulator has prompted a re-evaluation of the role of bone mineralization factors in the development of metabolic disease.Enpp1(-/-) mice exhibited mildly improved glucose homeostasis on a normal diet but showed a pronounced resistance to obesity and insulin resistance in response to chronic high-fat feeding.A fuller understanding of the pathways of NPP1 could inform the development of novel therapeutic strategies for treating insulin resistance.
Affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh, EH25 9RG, UK.Show MeSH
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Mentions: Owing to the recognized inhibitory activity of NPP1 on the insulin receptor (Maddux and Goldfine, 2000), we tested whether global deletion of Enpp1 would translate into changes in whole-body glucose metabolism. Adult Enpp1−/− mice showed normal glucose tolerance tests (GTTs) (Fig. 2A,D) but with a lower glucose-stimulated insulin secretion (GSIS) peak across the GTT, indicating insulin sensitization (Fig. 2B,D). Adult Enpp1−/− mice also showed normal insulin tolerance tests (ITTs) (Fig. 2C,D) and there were no differences in the size or number of insulin-secreting islets in the pancreas of Enpp1−/− mice compared with WT (Fig. 3E,F).
Affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh, EH25 9RG, UK.