Glucose, Glucose Transporters And Blastocyst Formation In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$281,650.00
Summary
Embryo-based biotechnologies have the potential to improve human reproductive health, notably in treating infertility by In vitro fertilisation (IVF). They are also central to the future use of embryonic stem cells for human tissue replacement. This project investigates the molecular mechanisms controlling one of the earliest differentiations in the growth of the embryo. Using the mouse as an experimental model it will investigate the importance of several factors in the changes which set up the ....Embryo-based biotechnologies have the potential to improve human reproductive health, notably in treating infertility by In vitro fertilisation (IVF). They are also central to the future use of embryonic stem cells for human tissue replacement. This project investigates the molecular mechanisms controlling one of the earliest differentiations in the growth of the embryo. Using the mouse as an experimental model it will investigate the importance of several factors in the changes which set up the placenta and fetus as seperate tissues in the very early embryo. A key focus is the supply of glucose to the newly fertilised embryo and how important this glucose supply is for the survival of the embryo. Moreover there is great interest in the possibility that metabolic events in utero can contribute to the development of diseases in later life, notably, coronary heart diease, stroke, high blood pressure and non-insulin dependent diabetes. The results from these studies will contribute to our understanding of why some couples are infertile, lead to improved management of infertility by diet and invitro fertilisation procedures. It will also be of benefit in dietary advice to women with diabetes mellitus, seeking to have children. The adenoviral strategy for gene delivery into early mouse embryos may in the long term also find wide clinical application in the treatment of genetic defects at the very earliest stages in development and as such is of enormous potential benefit in the management of both animal and human reproduction.Read moreRead less
Function And Pathophysiological Role Of A Novel Glucose Transporter Expressed In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$216,412.00
Summary
Diabetes is a disorder of metabolism resulting from a combination of deficiency of insulin and defective action of the insulin that is present. The most prominent metabolic abnormality is high blood glucose, which is often not satisfactorily corrected by insulin treatment. One of the main reasons for the high blood glucose is reduced uptake of glucose by muscle tissue. The mechanism by which insulin enhances glucose entry into muscle cells involves mobilisation of a specific protein from the glu ....Diabetes is a disorder of metabolism resulting from a combination of deficiency of insulin and defective action of the insulin that is present. The most prominent metabolic abnormality is high blood glucose, which is often not satisfactorily corrected by insulin treatment. One of the main reasons for the high blood glucose is reduced uptake of glucose by muscle tissue. The mechanism by which insulin enhances glucose entry into muscle cells involves mobilisation of a specific protein from the glucose transporter protein family, which has been designated GLUT4. Surprisingly, animals that have been genetically altered to eliminate orknockout GLUT4 production do not develop diabetes. This finding has led to the theory that there is a backup glucose transporter protein that can prevent diabetes when there is a problem with GLUT4 function. We have recently discovered a new member of the glucose transporter protein family that could potentially function as either a parallel or a backup system for GLUT4. This new glucose transporter, which we have called GLUT8, is present in human muscle tissue and studies in other cells have shown that it alters its distribution within the cell in reponse to insulin. We now want to study in more detail the role of this new glucose transporter in muscle tissue and how it functions compared with GLUT4. In particular, we think it is possible that Type 2 diabetes occurs when there is not only a problem with the mobilisation of GLUT4 but also a defect in the production or function of GLUT8. If this is the case, then increasing GLUT8 production might improve glucose transport into muscle tissue and so improve control of blood glucose levels in diabetes.Read moreRead less
Cellular Mechanisms And Physiological Roles Of GLUT12 Mediated Glucose Transport In Glucose Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$499,000.00
Summary
Diabetes affects almost one million Australians, although only 50% are aware they have the disease. Type 2 diabetes accounts for about 90% of diabetes and usually occurs after the age of 40. As a leading cause of death, adult blindness, lower limb amputation, kidney failure, stroke and heart attack, diabetes has huge economic and social consequences and has been designated an Australian National Health priority. A clinical feature of Type 2 diabetes is high blood glucose levels. This occurs beca ....Diabetes affects almost one million Australians, although only 50% are aware they have the disease. Type 2 diabetes accounts for about 90% of diabetes and usually occurs after the age of 40. As a leading cause of death, adult blindness, lower limb amputation, kidney failure, stroke and heart attack, diabetes has huge economic and social consequences and has been designated an Australian National Health priority. A clinical feature of Type 2 diabetes is high blood glucose levels. This occurs because insulin does not effectively stimulate the transfer of glucose from the blood into muscle and fat. The reasons for this are not fully understood. Insulin normally works to move glucose transporter (GLUT) proteins to the surface of muscle and fat cells. One GLUT that has been studied extensively in muscle and fat is GLUT4. GLUT4 moves to the cell surface in response to insulin and this response is one of the defects that is known to occur in Type 2 diabetes. Glucose then accumulates in the blood, leading to many of the complications of diabetes. We have discovered a novel glucose transporter, GLUT12, that is also present in muscle and fat. We have shown that GLUT12, like GLUT4, responds to insulin. GLUT12 could therefore be a critical backup for GLUT4. We have also found that GLUT12 responds to glucose itself, suggesting a unique role in controlling blood glucose levels. We will explore how GLUT12 acts in muscle and fat cells to find whether GLUT12 can act as a backup for GLUT4. We will also study GLUT12 in tissue from normal animals and in animals with features of Type 2 diabetes. To determine the role of GLUT12 in maintaining normal blood glucose levels, we will produce mice with an inactive GLUT12 gene. Our research could identify novel ways of increasing GLUT12 activity. The eventual goal will be to find a pharmaceutical compound that can improve glucose transport into muscle, reduce high blood glucose levels and thus the complications of Type 2 diabetes.Read moreRead less