The Role Of Androgens In Osteoblast Development And Bone Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
Male hormones are essential for the growth and maintenance of bone in men, but exactly how and when they act on the bone forming cells is unclear. We aim to find out what happens when the target for male hormones (receptor) is removed in the bone forming cells at different stages of their development. This project will increase our understanding of how male hormones regulate bone formation and may assist in the design of new therapies for osteoporosis.
The Effect Of PKC Epsilon On The Insulin Receptor And Whole Body Glucose Homeostasis.
Funder
National Health and Medical Research Council
Funding Amount
$82,261.00
Summary
Increased fat availability is strongly associated with insulin resistance and type 2 diabetes. Data from this lab has shown animals lacking a particular enzyme (Protein Kinase C epsilon) are able to compensate for this insulin resistance and maintain normal blood glucose levels by elevating insulin availability, with a major site of action being the liver. This project therefore aims to examine the action of PKC epsilon on insulin clearance by the liver.
Investigation Of Transgenic Mouse Models Of Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$412,200.00
Summary
Type 2 diabetes is a common condition characterised by high blood glucose, that afflicts 700,000 Australians. It causes blindness, kidney failure and an increased risk of heart attack and stroke. despite intensive study over many years, the reasons for the elevated blood glucose in this condition are not fully understood. Several abnormalities can contribute to the high glucose and different researchers have proposed different defects as the initial cause. It has proven difficult to unravel the ....Type 2 diabetes is a common condition characterised by high blood glucose, that afflicts 700,000 Australians. It causes blindness, kidney failure and an increased risk of heart attack and stroke. despite intensive study over many years, the reasons for the elevated blood glucose in this condition are not fully understood. Several abnormalities can contribute to the high glucose and different researchers have proposed different defects as the initial cause. It has proven difficult to unravel the sequence of events in the evolution of the syndrome because high glucose can cause insulin resistance and a defect in insulin secretion, both of which can lead to high blood glucose. One approach to study the consequences of specific defects is to genetically engineer them. The aims of this project are to: 1. make a mouse with reduced ability to store glucose in muscle. 2. test the metabolic consequences of a defect in the manufacture of glycogen (starch) in muscle. 3. study the effects of combining a defect in glucose storage with one that results in an oversupply of glucose. 4. study the effects on a mouse with a genetic predisposition for failure of beta cells (insulin making cells) of a defect in muscle glucose storage and over production of glucose. A successful completion of this grant will greatly enhance our understanding of how blood glucose is increased in Type 2 diabetes.Read moreRead less
The Mechanisms Of The Anabolic Actions Of Androgens In Bone.
Funder
National Health and Medical Research Council
Funding Amount
$470,960.00
Summary
Androgens (male sex hormones) are one of the few agents that increase bone formation. Androgens act by binding to a specific protein, the androgen receptor (AR). To understand exactly how androgens increase bone formation, we will study mice in which the AR is inactivated only in bone forming cells at specific stages of their development. Understanding the way in which androgens act on bone to increase size and strength will be of great benefit in the design of new treatments for osteoporosis.
Osteoporosis is a major health burden resulting from bone fractures in older men and women due to progressive loss of bone and weakening of the skeleton. No current treatment effectively reverses this bone loss. Using genetic models in mice, we have identified a pathway, involving the nerve signal molecule NPY, that is capable of inducing large (200 - 300%) increases in bone very rapidly (within a few weeks), in the skeleton of adult mice. This proposal is aimed at characterising this new pathwa ....Osteoporosis is a major health burden resulting from bone fractures in older men and women due to progressive loss of bone and weakening of the skeleton. No current treatment effectively reverses this bone loss. Using genetic models in mice, we have identified a pathway, involving the nerve signal molecule NPY, that is capable of inducing large (200 - 300%) increases in bone very rapidly (within a few weeks), in the skeleton of adult mice. This proposal is aimed at characterising this new pathway to assess its potential to provide new treatments for human osteoporosis. This research is important because of the size, rapidity and inducibility of the effect. Moreover, since it originates in the brain, it represents a quite novel mechanism by which the skeleton is potentially maintained and repaired. The experiments contained in the initial sections of the proposal are designed to assess not only the ability of the NPY-pathway to protect against bone loss but also to examine the possibility of repair to a fragile skeleton. The bone loss models chosen for study represent postmenopausal and age-related osteoporosis, two prevalent and increasingly common conditions in the aging world population. The latter section of the proposal seeks to clarify the mechanism by which the increase in bone formation occurs within the bone. Understanding the working of this pathway will be vital in developing future treatment regimens. This proposal investigates a novel, powerful and rapid pathway for repairing weakened skeletons. The knowledge resulting from this proposal has the potential to provide an important contribution to skeletal health and thus aged health worldwide.Read moreRead less