Regulation Of Pancreatic Beta-cell Number And Function By Adipocyte-released Hormones, Free Fatty Acids And Ghrelin.
Funder
National Health and Medical Research Council
Funding Amount
$256,500.00
Summary
The disease diabetes mellitus comprises a heterogeneous group of disorders all characterised by high blood glucose levels. Beta-cells in the pancreas, which secrete insulin, are central to the pathophysiology of the disease. Type 1 or insulin-dependent diabetes mellitus results from an absolute deficiency of insulin due to auto immunological destruction of the pancreatic beta cell, and accounts for 5-10% of total diabetes mellitus. In the more common type 2 or non-insulin-dependent diabetes mell ....The disease diabetes mellitus comprises a heterogeneous group of disorders all characterised by high blood glucose levels. Beta-cells in the pancreas, which secrete insulin, are central to the pathophysiology of the disease. Type 1 or insulin-dependent diabetes mellitus results from an absolute deficiency of insulin due to auto immunological destruction of the pancreatic beta cell, and accounts for 5-10% of total diabetes mellitus. In the more common type 2 or non-insulin-dependent diabetes mellitus, liver, muscle and fat cells are resistant to the action of insulin and compensatory mechanisms that are activated in the beta-cell to increase insulin secretion are not sufficient to maintain normal blood glucose levels. In Western countries including Australia, type 2 diabetes currently affects around 2% of the whole population and about 6% of adults (10% of over 60-y) and continues to grow at around 6% per annum. Type 2 diabetes often occurs in obese patients and a direct link between obesity and type 2 diabetes has been strongly suggested by research to date. It has also been found that a progressive loss of beta-cell function throughout the course of the disease results in the reduction of insulin secretion. The contribution of excessive fat tissue in obese patients to the progress of type 2 diabetes is not clear. Certain hormones from fat cells, metabolic regulatory hormone, and fatty acids have been demonstrated to influence the function of beta-cells in previous studies, including our own. We now aim to investigate in detail the effect of these on cultured beta-cells with molecular and cell biology techniques. We expect to identify a factor or factors which stimulate or inhibit the progress of beta-cell dysfunction, with the potential to identify therapeutic targets in the treatment of type 2 diabetes.Read moreRead less
Type 2 diabetes is reaching epidemic proportions across the world and is a huge burden in health care costs. We know it is a multifaceted disease with many symptoms, one of which is a reduction in insulin secretion. This proposal sets out to determine the mechanisms of insulin secretion from healthy tissue and what goes wrong in disease.
Secretion is an essential step in memory and learning, control of metabolism and reproduction and the functioning of most organs. Secretory dysfunction also underlies many diseases including type 2 diabetes. We plan experiments to test for a new model of control of insulin secretion.
Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine ....Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine the importance of a family of intracellular signalling enzymes, the Class II phosphoinositide 3-kinases, in platelet function. These studies will define the contribution of these enzymes to platelet production and function and will establish whether their inhibition is an attractive strategy for the prevention of arterial thrombosis.Read moreRead less
Diet-induced obesity is the foremost health concern in today�s society and causes many metabolic problems that lead to type diabetes and cardiovascular disease. This grant identifies ghrelin resistance, as a novel metabolic adaptation during obesity. Ghrelin is a hormone that normally stimulates food intake and body weight gain, however during obesity ghrelin does not stimulate food intake. Artificial induction of ghrelin resistance will restrict the development of diet _induced obesity.
Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in ....Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in the levels of nitric oxide in the body are associated with several diseases states and states of dysfunction including cardiovascular disease, diabetes and also impotence. Professor Triggle's study seeks to characterize how tissues may store nitric oxide, thus prolonging the life of nitric oxide, and how such stores are released. Read moreRead less
Adrenergic Activation Of Brown Adipose Tissue In Humans.
Funder
National Health and Medical Research Council
Funding Amount
$323,301.00
Summary
Obesity is a major health and financial threat to society in the near future, thus new anti-obesity therapies are essential. Activation of brown adipose tissue (BAT) can increase resting energy expenditure by 20%, and its recent conclusive identification in adults renewed interest in its potential as an anti-obesity target. We will determine whether BAT can be activated pharmacologically in humans, whether obesity reduces its activity and if long-term drug treatment can increase BAT function.
Identifying novel roles of disease-related proteins in the regulation of exocytosis and nervous communication. This research aims to identify new molecules involved in regulating nerve communication and hormone secretion and which are relevent to human diseases and conditions including Type 2 Diabetes, Down Syndrome, Alzheimer's Disease and Huntington's Disease. The findings may provide new targets in the treatments of such conditions. This research is therefore of special relevance to National ....Identifying novel roles of disease-related proteins in the regulation of exocytosis and nervous communication. This research aims to identify new molecules involved in regulating nerve communication and hormone secretion and which are relevent to human diseases and conditions including Type 2 Diabetes, Down Syndrome, Alzheimer's Disease and Huntington's Disease. The findings may provide new targets in the treatments of such conditions. This research is therefore of special relevance to National Research Priority 2: Promoting and Maintaining Good Health and especially to the sub-areas of this Research Priority 2: Ageing well, ageing productively and Preventative healthcare.Read moreRead less
Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studi ....Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studies to investigate the effects of drugs that affect estrogen action and environmental estrogens. Read moreRead less