Which Transgenic Pig Will Be Used For Islet Transplantation In Humans?
Funder
National Health and Medical Research Council
Funding Amount
$3,031,083.00
Summary
We propose that xenotransplantation of pig islets will cure Type 1 diabetes. This program will generate genetically modified pigs to overcome the molecular differences between pigs and humans by removing a pig gene and inserting several human genes. In addition, we will add immunosuppressive genes and so minimise the need for drug treatment of the diabetic recipient. We will test our hypothesis by transplanting islets from these genetically modified pigs into baboons. We suggest that this will p ....We propose that xenotransplantation of pig islets will cure Type 1 diabetes. This program will generate genetically modified pigs to overcome the molecular differences between pigs and humans by removing a pig gene and inserting several human genes. In addition, we will add immunosuppressive genes and so minimise the need for drug treatment of the diabetic recipient. We will test our hypothesis by transplanting islets from these genetically modified pigs into baboons. We suggest that this will provide an inexhaustible supply of islets for transplantation.Read moreRead less
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.
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.
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.
The Role Of The Novel Gene Herpud1 In Insulin Secretion In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$502,370.00
Summary
A reduced ability to secrete insulin is the cause of high blood sugar in type 2 diabetes. This study has identified a gene called Herpud1 that affects insulin secretion. By studying the effects of this gene we are improving our knowledge of the defects that occur in Type 2 diabetes. This has the potential of providing better therapeutic strategies and identifying targets for the developments of better drug development.
Role Of Islet ?-cell Failure In The Pathogenesis Of Non-alcoholic Steatohepatitis
Funder
National Health and Medical Research Council
Funding Amount
$560,111.00
Summary
Some people respond to obesity poorly developing diseases such as non-alcoholic steatohepatitis (NASH) and diabetes. Other people do not, safely storing the excess energy in non-abdominal fat. The applicants will study 2 obese strains of mice; one develops “adipose tissue restriction”, NASH and diabetes, the other does not. The hypothesis that failure of compensatory insulin secretion to over-nutrition is an upstream event causing adipose tissue restriction, followed by NASH, will be tested.
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.
RCAN1 IS A MASTER REGULATOR OF BETA CELL FUNCTION AND INSULIN SECRETION
Funder
National Health and Medical Research Council
Funding Amount
$446,610.00
Summary
Type 2 diabetes affects over 1.5 million Australians and is caused by insufficient insulin release by beta cells in the pancreas. We have discovered a new regulator of insulin secretion called RCAN1 and we now aim to understand how this regulation occurs. We also believe RCAN1 may be responsible for the transition from healthy to dysfunctional beta cell in Type 2 diabetes and this project will identify whether this is the case.