Investigating The Novel Role Of SEPS1 In The Prevention Of Islet Beta Cell Failure And Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$535,804.00
Summary
SEPS1 is an important glucose-regulated protein whose function is to protect tissues from oxidative stress. Inhibition of SEPS1 by hyperglycaemia, is a mechanism for progression of Type 1 and Type 2 diabetes once hyperglycaemia supervenes. The overall aim of the project is to investigate the function of the novel SEPS1, using transgenic and knockout approaches.
Do Synaptic-like Mechanisms Control Insulin Secretion?
Funder
National Health and Medical Research Council
Funding Amount
$593,235.00
Summary
An estimated 415 million people world-wide were diagnosed with diabetes in 2015. One of the causal factors in disease is the dysregulation of insulin secretion. We have developed new techniques to study insulin secretion that has led us to propose a new model for secretory control. This proposal sets out experiments to critically test this model. The outcomes could have wide-reaching impact on understanding and for future treatment and prevention of the diabetes.
Transplantation of pancreatic islets is the only cure for type 1 diabetes (T1D). Unfortunately, many of the transplanted islet cells die quickly due to an inadequate supply of blood. Herein, we investigate a novel cell surface protein for its role in islet and blood vessel survival and function. Furthermore, we use nanotechnology to provide said protein to the islet cells during transplantation for increased survival and function. Ultimately, this work may cure more patients with diabetes.
Endothelial And Mesenchymal Cell Interactions In Pancreatic Beta Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$95,583.00
Summary
Type 1 diabetes is a condition that arises when the body's immune system destroys insulin-producing beta cells within the pancreas. Recent studies have shown that normal glucose control can be restored by replacing the missing beta cells by transplantation of cells from deceased donors. However, the demand for transplant material outweighs supply. The work described in this application seeks to define how insulin-producing beta cells can be derived in the laboratory from embryonic stem cells.
Targeting Insulin Hypersecretion To Prevent Type 1 And Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$834,596.00
Summary
Diabetes develops when islet beta-cells fail to secrete insulin. While major differences exist in the mechanisms by which type 1 and type 2 diabetes develop, there is overlap in beta-cell susceptibility factors. We will investigate whether an islet 'overwork' response to excess nutrient loads underlies beta-cell susceptibility to failure in both types of diabetes. We will also develop novel pharmacological approaches to reduce islet 'overwork' to prevent and treat type 1 and 2 diabetes.
The Structure And Function Of The Apical Domain In Insulin Secreting Beta Cells.
Funder
National Health and Medical Research Council
Funding Amount
$571,741.00
Summary
Loss of control of insulin secretion is causal in diabetes and therefore its understanding is a key goal to shed light on the disease. We have recently identified a new domain in the insulin secreting cells, called the apical domain. This proposal will define the role of this apical domain in controlling insulin secretion. The outcomes could provide new insights into how diabetes develops and new targets for therapies.
Mechanism Of Protection Of Islet Beta Cells From T1D By Heparan Sulfate
Funder
National Health and Medical Research Council
Funding Amount
$602,453.00
Summary
Type 1 diabetes (T1D) is an autoimmune disease which destroys the insulin-producing beta cells in the pancreas. Current insulin therapy does not prevent the development of serious secondary complications. We have discovered that beta cells require a complex sugar (heparan sulfate; HS) for their survival and that T1D is prevented when an enzyme, heparanase, that degrades HS is inhibited. Understanding these mechanisms will identify new therapeutic strategies for preventing T1D progression.
Glucose Toxicity-induced Activation Of The Bcl-2-regulated Apoptotic Pathway In Pancreatic Beta Cells
Funder
National Health and Medical Research Council
Funding Amount
$617,238.00
Summary
High blood glucose or hyperglycaemia is a feature of type 2 diabetes. Hyperglycaemia and fatty acids in the blood can cause damage of the insulin-producing pancreatic beta cells, resulting in worsening of diabetes. We plan to elucidate the pathways in beta cells that are stimulated by high levels of glucose and fatty acids, and to determine if these pathways are turned on in the pancreas of patients with type 2 diabetes, to try and identify targets for new therapies.
Investigating FABP4 As An Insulinotropic Adipokine
Funder
National Health and Medical Research Council
Funding Amount
$518,128.00
Summary
Obesity is an epidemic: 1 in 4 Australian adults and 1 billion people on earth are obese, with diabetes, heart disease and cancer closely linked. Our study will reveal how the novel hormone Fatty acid binding protein 4 is released from fat and enhances pancreatic insulin secretion in response to obesity. This will explain how pathological increases in insulin levels occur during obesity (a longstanding conundrum) and provide new therapeutic targets with which to treat the disease.
A Novel Role For Alzheimer Tau Protein In Insulin Secretion And Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,023,712.00
Summary
There is a strong association between type 2 diabetes and Alzheimer's disease, however the reason for this is not known. In Azheimer's disease a protein called tau does not function normally and contributes to the declining cognitive function. We have shown that when tau is absent, this lowers blood glucose and reduces the hallmark defects that contribute to type 2 diabetes. By understanding how tau works we may be able to provide better therapeutic agents to treat type 2 diabetes.