Analysis Of The Role Of Vesicle Docking/Fusion Proteins In Trafficking Of The Glut4 Glucose Transporter In Adipocytes
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
The objective of these studies is to understand the molecular mechanisms that are involved in the control of blood glucose levels by the hormone insulin. Elevated blood glucose levels following a meal stimulate the pancreas to release insulin into the circulation. Insulin acts to reduce blood sugar levels by stimulating the uptake of glucose into fat and muscle and suppressing glucose production by the liver. Defects in insulin action in these tissues are the primary cause of Type II diabetes. T ....The objective of these studies is to understand the molecular mechanisms that are involved in the control of blood glucose levels by the hormone insulin. Elevated blood glucose levels following a meal stimulate the pancreas to release insulin into the circulation. Insulin acts to reduce blood sugar levels by stimulating the uptake of glucose into fat and muscle and suppressing glucose production by the liver. Defects in insulin action in these tissues are the primary cause of Type II diabetes. The debilitating effects of Type II diabetes, the dramatic increase its incidence, and the expense of treating the symptoms of diabetic complications have lead to the realization that the disease represents a major health problem requiring substantial research and development efforts. The project will focus on insulin regulation of glucose uptake in fat cells. Insulin promotes glucose uptake into fat by activating an intracellular signaling pathway that triggers the translocation of a unique glucose transporter protein (Glut4) from storage sites inside the cell to the cell surface. Glut4 translocation is mediated by small membrane vesicles that function to sequester the glucose transporter inside cells in the absence of insulin, and to shuttle Glut4 to the cell surface in response to the hormone. Despite the central importance of this event to the maintenance of normal blood glucose levels, it is poorly understood. The studies will be directed towards investigating the cellular machinery involved in the latter stages of insulin-stimulated glucose uptake- the vesicle-mediated delivery of Glut4 to the cell surface. The objective of these studies is to better understand the molecular basis for Glut4 translocation, and regulation by the insulin signaling cascade. Accomplishment of this goal may suggest potential drug intervention strategies aimed at enhancing insulin-stimulated Glut4 translocation and promoting improved control of blood glucose levels in Type II diabetes.Read moreRead less
Analysis Of Intracellular Signalling And Biological Activities Of The GM-CSF Receptor Family Using Constitutive Mutants
Funder
National Health and Medical Research Council
Funding Amount
$505,699.00
Summary
The cytokines GM-CSF, IL-3 and IL-5 stimulate the growth and actions of a wide range of blood cells. Each binds to a receptor on the cell surface which then triggers the generation of a number of signals inside the cell; it is these signals that are responsible for the cytokine?s actions. We have previously generated a panel of constitutive mutant forms of the beta subunit which is shared by the GM-CSF, IL-3 and IL-5 receptors. These constitutive mutants trigger signals even in the absence of th ....The cytokines GM-CSF, IL-3 and IL-5 stimulate the growth and actions of a wide range of blood cells. Each binds to a receptor on the cell surface which then triggers the generation of a number of signals inside the cell; it is these signals that are responsible for the cytokine?s actions. We have previously generated a panel of constitutive mutant forms of the beta subunit which is shared by the GM-CSF, IL-3 and IL-5 receptors. These constitutive mutants trigger signals even in the absence of the cytokine; importantly, the different mutants appear to trigger only a subset of the signals generated by the normal receptor. The aim of this project is to use our panel of constitutive beta subunit mutants to determine how the GM-CSF, IL-3 and IL-5 receptors generate signals inside the cell and how these signals lead to the various biological actions of the receptors on blood cell growth and maturation. Findings from this research will be relevant to the understanding and treatment of diseases which involve abnormal growth or function of blood cells such as leukaemia and inflammatory diseases.Read moreRead less
Regulation Of Body Composition And Glucose Homeostasis By The Adaptor Protein Grb10.
Funder
National Health and Medical Research Council
Funding Amount
$617,256.00
Summary
Resistance to the hormone insulin underlies the development of Type 2 Diabetes. Loss of muscle mass in the elderly contributes to insulin resistance. Recently we identified Grb10 as a new regulator of insulin action and muscle mass. In this proposal, we aim to study how Grb10 affects development and growth of muscle and fat, and the underlying molecular mechanisms. This may lead to new strategies for improving body composition and treating the insulin resistance associated with Type 2 Diabetes.