Unravelling The Mechanisms By Which Insulin Hypersecretion Is Detrimental To ß-cell Function And Survival In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$727,758.00
Summary
Type 2 diabetes is associated with reduced levels of the hormone insulin that results in an increase in blood sugar. Evidence suggests that when the cells that make insulin are overworked they fail to produce the right amount of this hormone to keep blood sugar levels normal. In this proposal we will determine how overworking the insulin producing cells damages them and assess whether reducing the need to overwork is beneficial and thus lead to reduced blood sugar levels in Type 2 diabetes.
Hypothalamic Signalling In Cortical And Trabecular Bone Anabolic Activity
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
Osteoporosis is a disease associated with an exponential rise in the number of fractures in the elderly. These fractures are so common that around 1 in 3 women and 1in four men will be affected. They cause pain, disability that can be permanent disability and are associated with premature death. Current treatments are able to effectively increase bone strength in osteoporotic patients but can not return bone strength to normal. Some new treatments can restore bone strength to some extent but the ....Osteoporosis is a disease associated with an exponential rise in the number of fractures in the elderly. These fractures are so common that around 1 in 3 women and 1in four men will be affected. They cause pain, disability that can be permanent disability and are associated with premature death. Current treatments are able to effectively increase bone strength in osteoporotic patients but can not return bone strength to normal. Some new treatments can restore bone strength to some extent but these are limited by expense and safety concerns. We have discovered a pathway in the brain that reduces bone formation and by blocking this pathway we can achieve doubling of the amount of bone in key bone sites. This occurs due to a marked increase in the amount of new bone formed. In fact, genetic manipulation of this pathway was able to double the speed at which bone is made by the skeleton. Excitingly, these increases in bone were possible in adult mice, suggesting such changes could be potential therapy for human patients. However, in order to be able to harness this pathway we must understand what molecules within the brain are responsible for the signals that reach the bone. Our proposal aims to identify the nerve signalling molecule(s) and the receptor for these signals within the brain that initiates the increase in bone formation. This project ultimately aims to identify a target for new therapies that could cause this beneficial effect by administration of a simple treatment, preferably by mouth in adult humans.Read moreRead less
Correction Of Diabetes In An Autoimmune Model Using Insulin-secreting Liver Cells.
Funder
National Health and Medical Research Council
Funding Amount
$472,500.00
Summary
Type I diabetes mellitus is caused by the autoimmune destruction of the beta cells of the pancreas that secrete insulin. The problems of the chronic complications of diabetes and the lack of donor tissue for transplantation, could theoretically be overcome by engineering from the patient's own cells, an artificial beta cell, i. e. a non-islet cell capable of synthesising, storing and secreting mature insulin in response to metabolic stimuli, such as glucose. The ultimate goal of this technology ....Type I diabetes mellitus is caused by the autoimmune destruction of the beta cells of the pancreas that secrete insulin. The problems of the chronic complications of diabetes and the lack of donor tissue for transplantation, could theoretically be overcome by engineering from the patient's own cells, an artificial beta cell, i. e. a non-islet cell capable of synthesising, storing and secreting mature insulin in response to metabolic stimuli, such as glucose. The ultimate goal of this technology is to deliver the insulin gene directly to a patient's own liver cells which would regulate insulin secretion in response to glucose and other substances that stimulate insulin secretion, controlling blood glucose without the need for immunosuppression. To accomplish this it must be possible to deliver the insulin gene efficiently to primary liver cells (cells derived from an animal's or human's body). Results from our laboratory using a non-pathogenic viral delivery system indicate that we can reverse diabetes in chemically induced diabetic rats by expression of insulin and a beta cell transcription factor NeuroD. The aim of this study is to repeat this in an auto-immune model of diabetes the nonobese diabetic mouse, which mimicks very closely the development of diabetes in humans. We will determine if we can reverse diabetes in these animals and determine if their response to glucose is normal over an extended period of time, with no attack by the factors of the immune system that stimulate the development of diabetes in man. The results from this research proposal should result in the delivery of the insulin gene to large numbers of primary liver cells that will then synthesise, store and secrete insulin in response to glucose. These cells would control blood glucose levels in patients without the need for immunosuppression.Read moreRead less