Defining The Insulin-signalling Defect In Human Insulin Resistance And Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$94,280.00
Summary
Problems with the way insulin removes glucose from the circulation contribute to developing type 2 diabetes. Despite research to date, controversy remains regarding the nature of known defects in insulin action and their relevance to humans. We plan to measure molecules involved in insulin action in muscle of people with insulin resistance, which is linked to diabetes. These studies will define new defects that cause insulin resistance and type 2 diabetes in humans.
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. Although there are currently therapies to reduce bone loss, no current treatment effectively reconstructs lost bone. In this project, which is designed to identify new genes that may in the future be targeted by drugs to reverse osteoporosis, we have identified specific sets of genes that appear to work together to increase bone formation. This ....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. Although there are currently therapies to reduce bone loss, no current treatment effectively reconstructs lost bone. In this project, which is designed to identify new genes that may in the future be targeted by drugs to reverse osteoporosis, we have identified specific sets of genes that appear to work together to increase bone formation. This proposal is aimed at characterising these genes and the ways in which they work to determine whether they may be good targets for new osteoporosis treatments. We will examine the patterns of these genes in bone. We will also use cell cultures in which bone forming cells develop and function, to determine when the genes are expressed and how they function. We will test the ability of the candidate genes to cause an increase in the amount of bone forming activity in these cell cultures. An increase in bone formation may be caused by an increase in the number bone-forming cells, an increase in the activity of the cells, a decrease in cell death, or a combination of these changes. Each possibility will be tested. This research is important because of the need for new osteoporosis therapies to repair weakened bones. 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
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
Regulation Of Insulin Signalling And Glucose Homeostasis By Protein Tyrosine Phosphatases
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
A common feature of type 2 diabetes is high blood glucose due to peripheral insulin resistance. Protein tyrosine phosphatases (PTPs) that antagonise insulin signalling might be important targets for therapeutic intervention in type 2 diabetes; inhibition of specific PTPs may allow for enhanced IR signalling to alleviate insulin resistance. This proposal will examine the roles of PTPs and in particular TCPTP in insulin signalling and glucose homeostasis.
Novel Regulators Of Glucose Metabolism And Inflammation In Adipose Tissue Of Females
Funder
National Health and Medical Research Council
Funding Amount
$282,830.00
Summary
Obesity is a common problem which can lead to development of diabetes and heart disease. One of the major mechanisms by which obesity leads to these diseases involves a defect in the ability of insulin to stimulate uptake of glucose into cells. We have found that excess of the sex hormone testosterone in women can contribute to this defect in tissues. This study will investigate why testosterone causes this defect in females and whether this defect can be prevented using existing drug therapies.
I am a cellular physiologist investigating the role of ion channels, receptors and intracellular signalling systems in the control of hormone secretion from endocrine cells, contraction of cardiac myocytes and to a lesser extent, growth of endometrium can
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.
Nutrient Dependent Signalling In Bone Via Calcium Sensing Receptors
Funder
National Health and Medical Research Council
Funding Amount
$226,650.00
Summary
Osteoporosis is a major health problem that affects as many as 10% of the Australian Community and costs the health budget millions of dollars each year. A number of key nutritional factors including calcium and dietary protein intake are known to be important in the development of osteoporosis. This proposal will test the hypothesis that human bone cells express a protein which senses calcium and amino acids, the calcium-sensing receptor, and thereby respond to nuritional signals arising from t ....Osteoporosis is a major health problem that affects as many as 10% of the Australian Community and costs the health budget millions of dollars each year. A number of key nutritional factors including calcium and dietary protein intake are known to be important in the development of osteoporosis. This proposal will test the hypothesis that human bone cells express a protein which senses calcium and amino acids, the calcium-sensing receptor, and thereby respond to nuritional signals arising from the presence of calcium ions and amino acids in plasma. Furthermore, we propose that by promoting osteoblast proliferation, maturation and survival, the calcium sensing receptor acts as the key molecular mechanism by which dietary calcium and protein promotes bone formation.These studies have potential to explain relationships between bpne resorptive activity, which raises local calcium concentrations, and bone formation activity and the coupling of bone forming and resorbing activity. These studies have the potential to explain the positive effects of calcium and protein intake on bone mass and may also shed light on the regulation of the coupling between osteoblastic and osteoclastic activityRead moreRead less