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.
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.
Inhibition Of Glucose-stimulated Insulin Secretion By Protein Kinase C Epsilon
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
Type 2 diabetes is a chronic disease which occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and is strongly linked to obesity. We have discovered that fat oversupply activates an enzyme in the pancreas causing defects in insulin release due to glucose. Inhibiting this enzyme helps overcome diabetes, through poorly defined mechanisms that we aim to clarify here. Our work could lead to new therapies for diabetes.
The Mechanism Of Growth Hormone Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$679,500.00
Summary
Growth hormone GH excess or deficit results in considerably shortened lifespan. While cardiovascular disease is a major element in this mortality, GH status has also been linked to kidney disease and diabetic retinopathy. Importantly, GH produced locally in breast cells and prostate cells transform s these cells, creating cancers. We aim to define how GH activates its receptor, to facilitate a GH antagonist which results from understanding how GH activates its cell surface receptor.
Adiponectin: Key Factors Determining Its Metabolic Actions And Influences On Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$604,793.00
Summary
Diabetes and obesity are growing at alarming rates due to poor lifestyle and other factors. Adiponectin is a complex molecule secreted by fat tissue that may help to burn fat in other tissues such as muscle and liver. We investigate what are the main determinants of adiponectin action and how these might counteract defective insulin action caused by excessive fat intake. This promises to provide new therapeutic targets to lessen the metabolic derangement associated with diabetes and obesity
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.