Hepatic Oxidative Stress, PTPs & STAT Signalling In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$1,086,547.00
Summary
Obesity is increasing at an alarming rate worldwide and is a leading cause of morbidity and mortality. Obesity is causally linked to the development of insulin resistance, a prelude to type 2 diabetes. In this proposal we will define a novel liver centric mechanism by which insulin resistance and oxidative stress may promote the development of morbid obesity, type 2 diabetes and liver disease.
Regulation Of Hypothalamic Insulin & Leptin Signalling By TCPTP
Funder
National Health and Medical Research Council
Funding Amount
$758,504.00
Summary
Insulin & leptin signal in the brain to lower blood glucose, suppress food intake, increase activity & increase energy expenditure. Obesity diminishes the abilities of insulin & leptin to signal. This proposal will determine if the enzyme TCPTP terminates insulin & leptin signaling in the brain. Our studies will provide insight into the molecular causes of obesity & may identify a novel therapeutic target for the treatment of obesity & type 2 diabetes.
Regulation Of Insulin Sensitivity By Reactive Oxygen Species
Funder
National Health and Medical Research Council
Funding Amount
$564,644.00
Summary
In morbid obesity and type 2 diabetes chronic levels of reactive oxygen species (ROS) are detrimental and diminish insulin's ability to maintain normal blood glucose levels. Paradoxically, ROS also promote insulin action by inhibiting enzymes known as protein tyrosine phosphatases (PTPs). This proposal will determine whether the promotion of ROS for the inhibition of PTPs early in the progression of type 2 diabetes may be of therapeutic benefit.
Regulation Of Insulin Signalling & Glucose Homeostasis By Protein Tyrosine Phosphatases
Funder
National Health and Medical Research Council
Funding Amount
$503,776.00
Summary
Type 2 diabetes has reached epidemic proportions afflicting roughly 6% of the adult population in Western society. Although the underlying genetic causes and the associated pathological symptoms are heterogenous, a common feature is high blood glucose due to peripheral insulin resistance. The molecular basis of insulin resistance is believed to be attributable to defects in insulin receptor (IR) signalling. The IR is a protein tyrosine kinase that phosphorylates itself and downstream substrates ....Type 2 diabetes has reached epidemic proportions afflicting roughly 6% of the adult population in Western society. Although the underlying genetic causes and the associated pathological symptoms are heterogenous, a common feature is high blood glucose due to peripheral insulin resistance. The molecular basis of insulin resistance is believed to be attributable to defects in insulin receptor (IR) signalling. The IR is a protein tyrosine kinase that phosphorylates itself and downstream substrates on tyrosine in response to insulin. Protein tyrosine phosphatases (PTPs) that dephosphorylate the IR and its substrates might be important targets for therapeutic intervention in type 2 diabetes; inhibition of specific PTPs may allow for enhanced insulin-induced signalling to alleviate insulin resistance. This proposal will examine the roles of PTPs and in particular TCPTP in IR signalling in vivo. Our studies will shed light on the molecular mechanisms of IR regulation and function and may provide important insights into novel strategies for enhancing insulin sensitivity in type 2 diabetes.Read moreRead less