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.
Investigation Of The Roles Of Protein Kinase C Epsilon In Insulin Secretion And Insulin Clearance
Funder
National Health and Medical Research Council
Funding Amount
$627,148.00
Summary
The rise in blood insulin levels after a meal normally reduces blood sugar levels by increasing glucose uptake and storage in certain tissues, especially muscle. Type 2 diabetes is characterized in part by a failure of the pancreas to produce adequate insulin in response to increases in blood sugar. This loss of insulin secretion has been strongly linked to increases in the availability of fat, although the reasons for this are not clear. We have recently found that mice lacking a specific enzym ....The rise in blood insulin levels after a meal normally reduces blood sugar levels by increasing glucose uptake and storage in certain tissues, especially muscle. Type 2 diabetes is characterized in part by a failure of the pancreas to produce adequate insulin in response to increases in blood sugar. This loss of insulin secretion has been strongly linked to increases in the availability of fat, although the reasons for this are not clear. We have recently found that mice lacking a specific enzyme (protein kinase C epsilon) are much less susceptible to the problems in dealing with blood sugar that are caused by a high fat diet. We showed that this is due partly to improved insulin secretion, and also to a slower breakdown of insulin by the liver, which increases its availability to target tissues. The aim of this project is to investigate the mechanisms occurring in the liver and in the pancreas by which this enzyme contributes to improved insulin action. Firstly, we will examine insulin uptake in liver cells, to investigate how the enzyme controls this process. Secondly, we will determine the mechanism through which the activation of the enzyme, upon increased fat supply to pancreatic beta-cells, reduces insulin secretion in response to glucose. Finally, will assess the relative importance of these two actions of the enzyme in improving the control of blood sugar levels. This work will lead to a better understanding of the mechanisms by which fat oversupply, and hence obesity, can play a role in the development of Type 2 diabetes, so that they can be targeted both for the development of new and more effective treatments for the disorder and for prevention of its onset.Read moreRead less
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.
Therapeutic Strategies And Screening Methods For PKC Epsilon Antagonists In The Treatment Of Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$157,375.00
Summary
Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown ....Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown that an enzyme found in the pancreas becomes inappropriately activated under conditions of fat oversupply, and plays an important role in the development of defects in insulin release from the pancreas in response to glucose. Excitingly, we have also shown that inhibition of this enzyme can partly reverse these defects once they have been established. We now intend to further validate this enzyme as a drug target by determining the optimum dosing regimen for the treatment of type 2 diabetes in a mouse model, and testing whether this approach can be used in conjunction with previously-developed drugs which promote insulin action, to improve bood glucose handling better than either treatment alone. This would promote the enzyme as a therapeutic strategy in the treatment of Type 2 diabetes. We also plan to develop a high throuhput screen to identify novel inhibitors of the enzyme, which will further increase the attractiveness of the project to pharmaceutical companies, who are better able to implent full commercialization of our findings.Read moreRead less
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.