The Structural Basis Of The Interaction Of Insulin-like Peptide 3, A Key Regulator Of Fertility, With Its Receptor.
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
The hormone, insulin-like peptide 3, has recently been shown to act directly on male and female germ cells to cause their maturation. It has considerable promise as a therapeutic agent for the regulation of fertility. Drugs based on the peptide may be used to assist in cases of infertility, and drugs that block its action have great potential as male and female contraceptives. Towards these goals, our project aims to understand how this peptide exerts its unique biological effects.
Muscarinic Receptor Signalling, Transglutaminase And Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$518,210.00
Summary
Diabetes is a major and increasing cuase of death and disability in our society. This studies aims to understand the cellular and molecular mechaisms controlling insulin secretion from the pancreas, since defects in this secretion are involved in causing diabetes. The proposed studies are of relevance to both juvenile and adult-onset diabetes, and may lead to new treatment modalities, as well as potentially being relevant to the use of pencreatic islet cell transplantation in the treatment of di ....Diabetes is a major and increasing cuase of death and disability in our society. This studies aims to understand the cellular and molecular mechaisms controlling insulin secretion from the pancreas, since defects in this secretion are involved in causing diabetes. The proposed studies are of relevance to both juvenile and adult-onset diabetes, and may lead to new treatment modalities, as well as potentially being relevant to the use of pencreatic islet cell transplantation in the treatment of diabetes.Read moreRead less
Molecular Pharmacology Of Beta Adrenoreceptors In Multiple Disease States
Funder
National Health and Medical Research Council
Funding Amount
$578,812.00
Summary
Obesity is a major and increasing health concern for almost half the adult population, and is associated with serious medical conditions including diabetes and heart disease. Changes in behaviour such as increasing physical activity and eating less high-calorie food help many people reduce their body weight, however many others have a genetic predisposition to become overweight and behavioural measures are ineffective. Although anti-obesity drugs should be a valuable adjunct to lifestyle changes ....Obesity is a major and increasing health concern for almost half the adult population, and is associated with serious medical conditions including diabetes and heart disease. Changes in behaviour such as increasing physical activity and eating less high-calorie food help many people reduce their body weight, however many others have a genetic predisposition to become overweight and behavioural measures are ineffective. Although anti-obesity drugs should be a valuable adjunct to lifestyle changes, the currently available appetite suppressants are not ideal. Our work involves studying particular cell-surface proteins (receptors) which normally respond to hormones such as adrenaline. The beta(3)-adrenergic receptor is known to mediate the breakdown of fats and increased heat production in adipose tissue and possibly muscle. Administration of beta(3)-selective drugs to obese mice promotes weight loss and a reduction of diabetic symptoms, and a number of drugs targetting the human beta(3)-adrenergic receptor are being developed by pharmaceutical companies. We are trying to understand more about the properties of this receptor, as this information will assist in designing drugs which are more selective and more potent. Sometimes drugs act at more than one receptor, and there is evidence that this may be the case for two drugs called CGP 12177 and BRL 37344 which stimulate the beta(3)-adrenergic receptor. The second major aim of our project is to find out whether these drugs act at a novel receptor which is related to the beta(3)-adrenergic receptor and also mediates energy expenditure and heat production in adipose tissue and skeletal muscle. The discovery of a new receptor would provide additional scope for the development of effective anti-obesity treatments.Read moreRead less
Actions Of Vanilloids In The Nucleus Of The Solitary Tract
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Capsaicin, the active ingredient of hot chillies, and other pungent plant extracts have been used for millennia to relieve minor pain. We now know that these agents produce pain relief (analgesia) by numbing the very nerve cells (neurons) which transmit pain signals to the brain. The unique analgesic properties of vanilloids may have a place in modern medicine, giving relief to sufferers of certain types of chronic pain (e.g., neuropathic pain) which are not responsive to morphine-like analgesic ....Capsaicin, the active ingredient of hot chillies, and other pungent plant extracts have been used for millennia to relieve minor pain. We now know that these agents produce pain relief (analgesia) by numbing the very nerve cells (neurons) which transmit pain signals to the brain. The unique analgesic properties of vanilloids may have a place in modern medicine, giving relief to sufferers of certain types of chronic pain (e.g., neuropathic pain) which are not responsive to morphine-like analgesics. Indeed, the promise of more potent and less pungent vanilloid analgesics has led to the discovery of numerous naturally-occurring and synthetic vanilloids. However, although the neurons which convey information regarding blood pressure and the oxygen content of arterial blood to control centres in the brain stem are also stimulated by vanilloids, the central (brain stem) actions of vanilloids on blood pressure and respiration have not been investigated in detail. Thus, the aim of this project is to describe the characteristics of vanilloid receptors in the brain stem, determine the acute and chronic effects of naturally-occurring and synthetic vanilloids on blood pressure and respiration, and elucidate the role played by other neurotransmitter chemicals in the actions of vanilloids. The results of these studies will have major implications in the future use of vanilloids as analgesics.Read moreRead less