Genetic activation of glycolysis in osteoblasts preserves bone mass in type I diabetes.
Cell Chem Biol
; 30(9): 1053-1063.e5, 2023 09 21.
Article
en En
| MEDLINE
| ID: mdl-37562406
ABSTRACT
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Experimental
/
Diabetes Mellitus Tipo 1
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Chem Biol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos