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Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes.

Huesa C, Zhu D, Glover JD, Ferron M, Karsenty G, Milne EM, Millan JL, Ahmed SF, Farquharson C, Morton NM, MacRae VE - Dis Model Mech (2014)

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.Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralization through the generation of pyrophosphate, and levels of NPP1 are elevated both in dermal fibroblast cultures and muscle of individuals with insulin resistance.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.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh, EH25 9RG, UK.

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Enpp1−/− mice exhibit insulin sensitization. (A) Glucose tolerance test (GTT). (B) Glucose-stimulated insulin secretion (GSIS). (C) Insulin tolerance test (ITT) represented as percentage (%) of basal glucose. (D) Metabolic tests analyzed as area under the curve. Mice were reared under control dietary conditions to 16 weeks of age. Results are presented as mean±s.e.m. (n=8). *P<0.05.
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f2-0071341: Enpp1−/− mice exhibit insulin sensitization. (A) Glucose tolerance test (GTT). (B) Glucose-stimulated insulin secretion (GSIS). (C) Insulin tolerance test (ITT) represented as percentage (%) of basal glucose. (D) Metabolic tests analyzed as area under the curve. Mice were reared under control dietary conditions to 16 weeks of age. Results are presented as mean±s.e.m. (n=8). *P<0.05.

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).


Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes.

Huesa C, Zhu D, Glover JD, Ferron M, Karsenty G, Milne EM, Millan JL, Ahmed SF, Farquharson C, Morton NM, MacRae VE - Dis Model Mech (2014)

Enpp1−/− mice exhibit insulin sensitization. (A) Glucose tolerance test (GTT). (B) Glucose-stimulated insulin secretion (GSIS). (C) Insulin tolerance test (ITT) represented as percentage (%) of basal glucose. (D) Metabolic tests analyzed as area under the curve. Mice were reared under control dietary conditions to 16 weeks of age. Results are presented as mean±s.e.m. (n=8). *P<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257003&req=5

f2-0071341: Enpp1−/− mice exhibit insulin sensitization. (A) Glucose tolerance test (GTT). (B) Glucose-stimulated insulin secretion (GSIS). (C) Insulin tolerance test (ITT) represented as percentage (%) of basal glucose. (D) Metabolic tests analyzed as area under the curve. Mice were reared under control dietary conditions to 16 weeks of age. Results are presented as mean±s.e.m. (n=8). *P<0.05.
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).

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.Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralization through the generation of pyrophosphate, and levels of NPP1 are elevated both in dermal fibroblast cultures and muscle of individuals with insulin resistance.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.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh, EH25 9RG, UK.

Show MeSH
Related in: MedlinePlus