PMID- 33116039
OWN - NLM
STAT- MEDLINE
DCOM- 20210721
LR  - 20210721
IS  - 1881-784X (Electronic)
IS  - 1881-7831 (Linking)
VI  - 14
IP  - 5
DP  - 2020 Nov 4
TI  - Effects of the linagliptin, dipeptidyl peptidase-4 inhibitor, on bone fragility 
      induced by type 2 diabetes mellitus in obese mice.
PG  - 218-225
LID - 10.5582/ddt.2020.03073 [doi]
AB  - 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.
FAU - Kanda, Junkichi
AU  - Kanda J
AD  - Department of Clinical Pharmacotherapy, Faculty of Pharmaceutical Sciences, 
      Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
FAU - Furukawa, Megumi
AU  - Furukawa M
AD  - General Health Medical Center, Yokohama University of Pharmacy, Yokohama, Japan.
FAU - Izumo, Nobuo
AU  - Izumo N
AD  - General Health Medical Center, Yokohama University of Pharmacy, Yokohama, Japan.
FAU - Shimakura, Taketoshi
AU  - Shimakura T
AD  - Niigata Bone Science Institute, Niigata, Japan.
FAU - Yamamoto, Noriaki
AU  - Yamamoto N
AD  - Niigata Bone Science Institute, Niigata, Japan.
AD  - Division of Orthopedic Surgery, Niigata Rehabilitation Hospital, Niigata, Japan.
FAU - Takahashi, Hideaki E
AU  - Takahashi HE
AD  - Niigata Bone Science Institute, Niigata, Japan.
FAU - Wakabayashi, Hiroyuki
AU  - Wakabayashi H
AD  - Department of Clinical Pharmacotherapy, Faculty of Pharmaceutical Sciences, 
      Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
LA  - eng
PT  - Journal Article
DEP - 20201029
PL  - Japan
TA  - Drug Discov Ther
JT  - Drug discoveries & therapeutics
JID - 101493809
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 104982-03-8 (Osteocalcin)
RN  - 3X29ZEJ4R2 (Linagliptin)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - EC 3.1.3.2 (Tartrate-Resistant Acid Phosphatase)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Bone Density/drug effects
MH  - Bone and Bones/abnormalities/*drug effects/metabolism
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/complications/*drug therapy
MH  - Dipeptidyl-Peptidase IV Inhibitors/administration & 
      dosage/*pharmacology/therapeutic use
MH  - Gastric Inhibitory Polypeptide/metabolism/pharmacology
MH  - Glucagon-Like Peptide 1/metabolism/pharmacology
MH  - Linagliptin/administration & dosage/*pharmacology/therapeutic use
MH  - Male
MH  - Mice
MH  - Mice, Obese
MH  - Osteocalcin/blood/drug effects
MH  - Tartrate-Resistant Acid Phosphatase/blood/drug effects
OTO - NOTNLM
OT  - Dipeptidyl peptidase-4 inhibitor
OT  - bone fragility
OT  - type 2 diabetes mellitus
EDAT- 2020/10/30 06:00
MHDA- 2021/07/22 06:00
CRDT- 2020/10/29 05:42
PHST- 2020/10/30 06:00 [pubmed]
PHST- 2021/07/22 06:00 [medline]
PHST- 2020/10/29 05:42 [entrez]
AID - 10.5582/ddt.2020.03073 [doi]
PST - ppublish
SO  - Drug Discov Ther. 2020 Nov 4;14(5):218-225. doi: 10.5582/ddt.2020.03073. Epub 
      2020 Oct 29.