Mitochondrial Sirtuins, Energy Metabolism And Insulin Action
Funder
National Health and Medical Research Council
Funding Amount
$582,925.00
Summary
Post-translational modification of lysine residues has a major influence on protein function. Many mitochondrial proteins are affected by lysine modifications and recent work has described a role for sirtuin enzymes in regulating these processes. This proposal will investigate whether targeted increases in sirtuin activity can improve mitochondrial function and insulin action in mouse models of obesity and insulin resistance.
Investigation Of The Mechanism By Which Medium Chain Fatty Acids Prevent The Development Of Obesity And Insulin Resistance - What Role For GPR84?
Funder
National Health and Medical Research Council
Funding Amount
$512,541.00
Summary
Medium chain fatty acids do not induce the same degree of obesity and insulin resistance as long chain fatty acids and this is due to changes in metabolism in skeletal muscle and adipose tissue. In this proposal we will investigate whether medium chain fatty acids induce their beneficial effects by interacting with a specific G protein-coupled receptor named GPR84. This receptor may be a new therapeutic target for the treatment of metabolic diseases.
Impact Of Islet Beta Cell Heparan Sulfate In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$576,777.00
Summary
Type 2 diabetes (T2D) is a chronic metabolic disease which ultimately leads to the death of insulin-producing islet beta cells, elevated blood sugar levels and daily insulin injections. Since beta cells require the complex sugar heparan sulfate (HS) for survival, we will investigate whether beta cell failure in T2D results from defective HS production. HS replacement will be evaluated as a new therapeutic strategy for preserving beta cell function and preventing the need for insulin injections.
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