Genetic activation of glycolysis in osteoblasts preserves bone mass in type I diabetes.
Glut1
Pfkfb3
Type I diabetes
bone
glucose
glycolysis
hyperglycemia
hypoinsulinemia
insulin
osteoblasts
Journal
Cell chemical biology
ISSN: 2451-9448
Titre abrégé: Cell Chem Biol
Pays: United States
ID NLM: 101676030
Informations de publication
Date de publication:
21 09 2023
21 09 2023
Historique:
received:
18
11
2022
revised:
18
05
2023
accepted:
16
07
2023
pmc-release:
21
09
2024
medline:
25
9
2023
pubmed:
11
8
2023
entrez:
10
8
2023
Statut:
ppublish
Résumé
Type I diabetes (T1D) impairs bone accrual in patients, but the mechanism is unclear. Here in a murine monogenic model for T1D, we demonstrate that diabetes suppresses bone formation resulting in a rapid loss of both cortical and trabecular bone. Single-cell RNA sequencing uncovers metabolic dysregulation in bone marrow osteogenic cells of diabetic mice. In vivo stable isotope tracing reveals impaired glycolysis in diabetic bone that is highly responsive to insulin stimulation. Remarkably, deletion of the insulin receptor reduces cortical but not trabecular bone. Increasing glucose uptake by overexpressing Glut1 in osteoblasts exacerbates bone defects in T1D mice. Conversely, activation of glycolysis by Pfkfb3 overexpression preserves both trabecular and cortical bone mass in the face of diabetes. The study identifies defective glucose metabolism in osteoblasts as a pathogenic mechanism for osteopenia in T1D, and furthermore implicates boosting osteoblast glycolysis as a potential bone anabolic therapy.
Identifiants
pubmed: 37562406
pii: S2451-9456(23)00231-3
doi: 10.1016/j.chembiol.2023.07.003
pmc: PMC10528964
mid: NIHMS1920550
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1053-1063.e5Subventions
Organisme : NIAMS NIH HHS
ID : P30 AR069619
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK125498
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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