| Source DB | nl |
|---|
| Institution | KU Leuven |
|---|
| Code | c97d799d-16d0-4113-af37-28e3024c86be |
|---|
| Unit | 61a9f0d7-1f47-46b1-9a91-25973d85f88e
|
|---|
| Begin | 1/1/2019 |
|---|
| End | 12/31/2022 |
|---|
| title fr |
|
|---|
| title nl | Cellulaire, moleculaire en endocriene mechanismen die de skeletale bijdrage tot de integratieve fysiologie reguleren
|
|---|
| title en | Cellular, molecular and endocrine mechanisms regulating skeletal contributions to integrative physiology
|
|---|
| Description fr |
|
|---|
| Description nl | We stellen hier voor om deze initiële bevinding te vervolgen door de mechanismen verder te ontrafelen waarmee osteolaire cellen in dit model de globale glucosehomeostase regelen en het therapeutisch potentieel te onderzoeken.
|
|---|
| Description en | The skeleton is increasingly recognized as a significant contributor to the regulation of whole-body processes, including energy metabolism. Much of this role has been ascribed to the endocrine actions of bone-derived osteocalcin (Ocn). Our recently published work, however, indicated that deletion of the hypoxia signalling pathway regulator Von Hippel-Lindau (Vhl) in osteoblast lineage cells led to alterations in systemic glucose homeostasis via effects that overruled the pronounced deficit in Ocn in these mice. These effects appeared to relate to the bone cells’ metabolism, with increased glycolysis and skeletal glucose uptake correlating with reduced glycemia. We here propose to follow up on this initial finding by further dissecting the mechanisms by which osteolineage cells in this model control global glucose homeostasis and exploring the therapeutic potential.Interestingly, Ocn has also been implicated in the endocrine regulation of cognition, anxiety and male reproduction. The very low Ocn serum levels in bone-targeted Vhl mutant mice warrant assessment of these extra-skeletal physiological functions, of their potential rescue by resupplementing Ocn, and of the mechanisms by which Vhl regulates Ocn. These studies may identify the hypoxia signaling pathway in osteolineage cells as upstream regulator of local Ocn production and its endocrine functions.This project will increase our understanding of integrated physiological responses, such as to ageing or bone disease.
|
|---|
| Qualifiers | - Endocrinolgy and diabetes - |
|---|
| Personal | Maes Christa |
|---|
| Collaborations | |
|---|
