FoxO1 expression in osteoblasts regulates glucose homeostasis through regulation of osteocalcin in mice.
Osteoblasts have recently been found to play a role in regulating glucose metabolism through secretion of osteocalcin. It is unknown, however, how this osteoblast function is regulated transcriptionally. As FoxO1 is a forkhead family transcription factor known to regulate several key aspects of glucose homeostasis, we investigated whether its expression in osteoblasts may contribute to its metabolic functions. Here we show that mice lacking Foxo1 only in osteoblasts had increased pancreatic beta cell proliferation, insulin secretion, and insulin sensitivity. The ability of osteoblast-specific FoxO1 deficiency to affect metabolic homeostasis was due to increased osteocalcin expression and decreased expression of Esp, a gene that encodes a protein responsible for decreasing the bioactivity of osteocalcin. These results indicate that FoxO1 expression in osteoblasts contributes to FoxO1 control of glucose homeostasis and identify FoxO1 as a key modulator of the ability of the skeleton to function as an endocrine organ regulating glucose metabolism.
Rached
Marie-Therese
MT
Department of Medicine, Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Kode
Aruna
A
Silva
Barbara C
BC
Jung
Dae Young
DY
Gray
Susan
S
Ong
Helena
H
Paik
Ji-Hye
JH
DePinho
Ronald A
RA
Kim
Jason K
JK
Karsenty
Gerard
G
Kousteni
Stavroula
S
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D054392:Adipokines / Q000502:physiology; D000818:Animals; D019556:COS Cells; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000473:pathology; D051379:Mice; D009765:Obesity / Q000517:prevention & control; D010006:Osteoblasts / Q000502:physiology*; D015675:Osteocalcin / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D015398:Signal Transduction
D054392:Adipokines; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D007328:Insulin; D015675:Osteocalcin; D000255:Adenosine Triphosphate; D017027:Protein Tyrosine Phosphatases; D005947:Glucose