Targeting Skeletal MTORC1 As A Novel Approach For The Treatment Of Diet-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$586,979.00
Summary
Diet-induced insulin resistance is a pathology that underlies type 2 diabetes. Elucidating the pathways and tissues that contribute to this condition is crucial for drug development. The skeleton has emerged as a critical insulin target tissue. We provide evidence that suppression of mTORC1, a complex over-activated by nutrients, in bone cells improves insulin sensitivity. In this study, we will determine if blocking mTORC1 function in bone cells can treat diet-induced insulin resistance.
How Does Osteocalcin Reverse Glucocorticoid-Induced Dysmetabolism?
Funder
National Health and Medical Research Council
Funding Amount
$635,038.00
Summary
The benefits of glucocorticoids (GCs) are often compromised by adverse effects such as bone loss, diabetes & obesity. There is now evidence that osteocalcin regulates fuel metabolism. Osteocalcin may therefore be a potential target to prevent the adverse metabolic effects of GC therapy. We aim to determine how osteocalcin regulates energy metabolism in adipose tissue and the liver under conditions of GC excess, and whether and how osteocalcin acts through a G-protein coupled receptor.
Bone mass is regulated by a number of processes that originate in the brain, however, the mechanism whereby the bone signals to the brain is unknown. Osteoblasts, the cells that form bone, secrete a hormone, osteocalcin that signals in other tissues to control energy and glucose homeostasis. This proposal explores osteocalcin signalling in bone as well as in the brain as a potential feedback from bone to the brain.