Effects of the linagliptin, dipeptidyl peptidase-4 inhibitor, on bone fragility induced by type 2 diabetes mellitus in obese mice.
Drug Discov Ther
; 14(5): 218-225, 2020 Nov 04.
Article
en En
| MEDLINE
| ID: mdl-33116039
ABSTRACT
Recently, it has been suggested that glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), which play important roles in the homeostasis of glucose metabolism, could be involved in the regulation of bone metabolism. Inhibitors of dipeptidyl peptidase 4 (DPP-4), an enzyme that degrades GIP and GLP-1, are widely used clinically as a therapeutic agent for diabetes. However, the effects of DPP-4 inhibitors on bone metabolism remain unclear. In this study, we investigated the effects of linagliptin, a DPP-4 inhibitor, on bone fragility induced by type 2 diabetes mellitus (T2DM). Non-diabetic mice were used as controls, and T2DM mice were administered linagliptin orally on a daily basis for 12 weeks. In T2DM mice, decreased bone mineral density was observed in the lower limb bones along with low serum osteocalcin levels and high serum tartrate-resistant acid phosphatase-5b (TRAP) levels. In contrast, the decreased serum osteocalcin levels and increased serum TRAP levels observed in T2DM mice were significantly suppressed after the administration of linagliptin 30 mg/kg. Bone histomorphometric analysis revealed a reduced osteoid volume and osteoblast surface with an increase in the eroded surface and number of osteoclasts in T2DM mice. This decreased bone formation and increased bone resorption observed in the T2DM mice were suppressed and trabecular bone volume increased following the administration of 30 mg/kg linagliptin. Collectively, these findings suggest that linagliptin may improve the microstructure of trabecular bone by inhibiting both a decrease in bone formation and an increase in bone resorption induced by T2DM.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Huesos
/
Diabetes Mellitus Tipo 2
/
Inhibidores de la Dipeptidil-Peptidasa IV
/
Linagliptina
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Drug Discov Ther
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón