Investigation Of Transgenic Mouse Models Of Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$412,200.00
Summary
Type 2 diabetes is a common condition characterised by high blood glucose, that afflicts 700,000 Australians. It causes blindness, kidney failure and an increased risk of heart attack and stroke. despite intensive study over many years, the reasons for the elevated blood glucose in this condition are not fully understood. Several abnormalities can contribute to the high glucose and different researchers have proposed different defects as the initial cause. It has proven difficult to unravel the ....Type 2 diabetes is a common condition characterised by high blood glucose, that afflicts 700,000 Australians. It causes blindness, kidney failure and an increased risk of heart attack and stroke. despite intensive study over many years, the reasons for the elevated blood glucose in this condition are not fully understood. Several abnormalities can contribute to the high glucose and different researchers have proposed different defects as the initial cause. It has proven difficult to unravel the sequence of events in the evolution of the syndrome because high glucose can cause insulin resistance and a defect in insulin secretion, both of which can lead to high blood glucose. One approach to study the consequences of specific defects is to genetically engineer them. The aims of this project are to: 1. make a mouse with reduced ability to store glucose in muscle. 2. test the metabolic consequences of a defect in the manufacture of glycogen (starch) in muscle. 3. study the effects of combining a defect in glucose storage with one that results in an oversupply of glucose. 4. study the effects on a mouse with a genetic predisposition for failure of beta cells (insulin making cells) of a defect in muscle glucose storage and over production of glucose. A successful completion of this grant will greatly enhance our understanding of how blood glucose is increased in Type 2 diabetes.Read moreRead less
Regulation And Effect Of The Growth Hormone, IGF-I, And IGF-Binding Protein Response To Acute Exercise
Funder
National Health and Medical Research Council
Funding Amount
$367,197.00
Summary
The body's ability to respond to physiological stress is vital to survival. This series of studies aims to examine the hormonal responses to physical exercise. In studies recently completed to determine how to detect Growth Hormone (GH) abuse in the Olympics, we have discovered a new system of hormones that respond to exercise. These Insulin-like Growth Factors (IGF) and their IGF-Binding Proteins (IGF-BP) are normally controlled by GH. The IGF-IGF-BP system normally acts to control of many cell ....The body's ability to respond to physiological stress is vital to survival. This series of studies aims to examine the hormonal responses to physical exercise. In studies recently completed to determine how to detect Growth Hormone (GH) abuse in the Olympics, we have discovered a new system of hormones that respond to exercise. These Insulin-like Growth Factors (IGF) and their IGF-Binding Proteins (IGF-BP) are normally controlled by GH. The IGF-IGF-BP system normally acts to control of many cellular and organ functions in many different tissues of the body. For example they stimulate protein accumulation and muscle growth, and have actions to control blood glucose in conditions like diabetes. Little is known about what regulates the production of the IGF and IGF-BPs in response to physical exercise. We aim to examine whether GH, either as an acute pulse as occurs naturally, or a direct effect of exercise that is not GH-mediated, is responsible for the increase in IGF and IGFBPs. This may uncover a new means of controlling this powerful hormonal system. In addition, we will examine whether GH or IGF-I, alone and together, influence the body's ability to respond to the stress of exercise (e.g., controlling fuel use, cardiovascular and kidney responses). Such information will allow greater understanding of this important hormonal system, so that in novel therapies may be developed for conditions such as normal ageing, the wasting states that accompany severe surgical or infectious stress, or conditions with abnormal blood glucose regulation such as diabetes. In addition, this information will permit greater sophistication in the detection of GH and related compounds in elite athletes. Unfortunately, GH is also being abused by non-elite athletes and high-school children. We believe our efforts will asist in the detection and prevention of these more general societal health issues.Read moreRead less