Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats
© 2018 Diabetes Canada Objective: Obese insulin resistance and type 2 diabetes mellitus profoundly impair bone mechanical properties and bone quality. However, because several antidiabetes drugs, especially thiazolidinediones, further aggravate bone loss in individuals with diabetes, diabetic osteop...
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th-cmuir.6653943832-583402018-09-05T04:36:56Z Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats Narattaphol Charoenphandhu Panan Suntornsaratoon Piangkwan Sa-Nguanmoo Pongpan Tanajak Jarinthorn Teerapornpuntakit Ratchaneevan Aeimlapa Nipon Chattipakorn Siriporn Chattipakorn Biochemistry, Genetics and Molecular Biology Medicine © 2018 Diabetes Canada Objective: Obese insulin resistance and type 2 diabetes mellitus profoundly impair bone mechanical properties and bone quality. However, because several antidiabetes drugs, especially thiazolidinediones, further aggravate bone loss in individuals with diabetes, diabetic osteopathy should not be treated by using simply any glucose-lowering agents. Recently, incretins have been reported to affect osteoblast function positively. The present study aimed to investigate the effects of vildagliptin, an inhibitor of dipeptidyl peptidase-4, on bone of rats with high-fat-diet-induced prediabetes. Methods: Male rats were fed a high-fat diet for 12 weeks to induce obese insulin resistance and then treated with vildagliptin for 4 weeks. The effects of the drug on bone were determined by microcomputed tomography and bone histomorphometry. Results: Vildagliptin markedly improved insulin resistance in these obese insulin-resistant rats. It also significantly increased volumetric bone mineral density. Specifically, vildagliptin-treated obese insulin-resistant rats exhibited higher trabecular volumetric bone mineral density than vehicle-treated obese insulin-resistant rats, whereas cortical volumetric bone mineral density, cortical thickness and area were not changed. Bone histomorphometric analysis in a trabecular-rich area (i.e. tibial metaphysis) revealed greater trabecular bone volume and number and less trabecular separation without change in trabecular thickness, osteocyte lacunar area or cortical thickness in the vildagliptin-treated group. Conclusions: Vildagliptin had a beneficial effect on the bone of obese insulin-resistant rats with prediabetes, particularly at the trabecular site. Such benefit probably results from enhanced bone formation rather than from suppressed bone resorption. 2018-09-05T04:22:52Z 2018-09-05T04:22:52Z 2018-01-01 Journal 23523840 14992671 2-s2.0-85044573817 10.1016/j.jcjd.2018.01.006 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85044573817&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/58340 |
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Biochemistry, Genetics and Molecular Biology Medicine Narattaphol Charoenphandhu Panan Suntornsaratoon Piangkwan Sa-Nguanmoo Pongpan Tanajak Jarinthorn Teerapornpuntakit Ratchaneevan Aeimlapa Nipon Chattipakorn Siriporn Chattipakorn Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats |
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© 2018 Diabetes Canada Objective: Obese insulin resistance and type 2 diabetes mellitus profoundly impair bone mechanical properties and bone quality. However, because several antidiabetes drugs, especially thiazolidinediones, further aggravate bone loss in individuals with diabetes, diabetic osteopathy should not be treated by using simply any glucose-lowering agents. Recently, incretins have been reported to affect osteoblast function positively. The present study aimed to investigate the effects of vildagliptin, an inhibitor of dipeptidyl peptidase-4, on bone of rats with high-fat-diet-induced prediabetes. Methods: Male rats were fed a high-fat diet for 12 weeks to induce obese insulin resistance and then treated with vildagliptin for 4 weeks. The effects of the drug on bone were determined by microcomputed tomography and bone histomorphometry. Results: Vildagliptin markedly improved insulin resistance in these obese insulin-resistant rats. It also significantly increased volumetric bone mineral density. Specifically, vildagliptin-treated obese insulin-resistant rats exhibited higher trabecular volumetric bone mineral density than vehicle-treated obese insulin-resistant rats, whereas cortical volumetric bone mineral density, cortical thickness and area were not changed. Bone histomorphometric analysis in a trabecular-rich area (i.e. tibial metaphysis) revealed greater trabecular bone volume and number and less trabecular separation without change in trabecular thickness, osteocyte lacunar area or cortical thickness in the vildagliptin-treated group. Conclusions: Vildagliptin had a beneficial effect on the bone of obese insulin-resistant rats with prediabetes, particularly at the trabecular site. Such benefit probably results from enhanced bone formation rather than from suppressed bone resorption. |
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Narattaphol Charoenphandhu Panan Suntornsaratoon Piangkwan Sa-Nguanmoo Pongpan Tanajak Jarinthorn Teerapornpuntakit Ratchaneevan Aeimlapa Nipon Chattipakorn Siriporn Chattipakorn |
author_facet |
Narattaphol Charoenphandhu Panan Suntornsaratoon Piangkwan Sa-Nguanmoo Pongpan Tanajak Jarinthorn Teerapornpuntakit Ratchaneevan Aeimlapa Nipon Chattipakorn Siriporn Chattipakorn |
author_sort |
Narattaphol Charoenphandhu |
title |
Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats |
title_short |
Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats |
title_full |
Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats |
title_fullStr |
Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats |
title_full_unstemmed |
Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats |
title_sort |
dipeptidyl peptidase-4 inhibitor, vildagliptin, improves trabecular bone mineral density and microstructure in obese, insulin-resistant, pre-diabetic rats |
publishDate |
2018 |
url |
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85044573817&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/58340 |
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