Understanding the role of Alzheimer’s tau protein in whole body glucose metabolism and type 2 diabetes
- Research Opportunity
- Number of Honour Places Available
- Medicine and Radiology
- Austin Health
|Dr Evelyn Marin||Personal web page|
|A/Prof Sof Andrikopoulos||Sof@unimelb.edu.au||Personal web page|
Overview There is a strong association between type 2 diabetes and Alzheimer’s disease: both diseases occur in older age and both have genetic causes. In Alzheimer’s disease microtubule-associated protein tau accumulates in neurofibrillary tangles and contributes to neurodegeneration. Initially, tau was thought to be a protein that was exclusive to nerves in the brain. However, new research suggests that tau is also highly abundant in the pancreas and other tissues of the body, where it interferes with the normal release of insulin and normal insulin action, contributing to diabetes. We think there is either too much tau, or, tau forms tangles that might also be causing diabetes by building up in the pancreas and other important tissues that control glucose metabolism. Therefore, this project will explore the role of the tau protein in glucose metabolism and diabetes. In this study we aim to understand: 1) In which organ(s) of the body does tau protein accumulate with aging? Is it the tau-tangles or just having too much tau that is bad for blood glucose control? What is driving tau protein higher- is it diabetes or obesity? 2) Does deleting all the tau protein from the body at birth protect the body from the defects that contribute to diabetes? How? To answer these questions, we will compare mice that develop diabetes to mice that don’t develop diabetes and measure tau proteins in all their tissues, something that is not possible in humans. We have a unique tool at our disposal, a tau knockout mouse, which lacks tau in its body from birth. We propose to treat mice with a high fat diet from 6 weeks old, to induce the early stages of diabetes (pre-diabetes) without actually causing diabetes. We want to know where and how the tau is accumulating in the mouse body and what pushes tau levels higher. Techniques: Blood glucose will be checked every fortnight to monitor the glucose levels. At the conclusion of the diets (3 months or 6 months old), mice will be subjected to various routine physiological tests such as glucose tolerance, glucose uptake in the tissues, insulin action and insulin secretion in the body of mice and tissues will be collected for immunohistochemistry, western blot and real time PCR studies.
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research
For further information about this research, please contact a supervisor.
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