Exploring the Role of Glycogen Structure in Type 2 Diabetes (2015–2019)
Given the rapidly increasing incidence of type 2 diabetes, a condition of poor blood glucose control that can cause a number of serious complications such stroke, coronary artery and peripheral vascular disease, amputations, renal failure, blindness and even death, it is important that we continue to search for new ways to help prevent and treat this disease. This project aims to explore our initial finding that diabetic mice have an impaired ability to form large glycogen particles, which has been shown to potentially result in poor blood glucose control. By expanding on this initial work, we will be able to better understand the mechanism by which diabetic mice are unable to form these particles, with the aim of being able to target key components in glycogen metabolism to make diabetic glycogen resemble that of healthy. This will involve administering diabetic mice with leptin, a hormone able to control their eating behaviour. Whether or not diabetic mice with a controlled eating behaviour start to resemble healthy mice in their liver-glycogen structure will give important insight into the cause of the differences seen between healthy and diabetic glycogen. Another important aspect of this work will be comparing the level of key enzymes involved in glycogen metabolism between healthy and non-diabetic mice. We also propose to perform the first experiments that compare the structure of healthy and
diabetic liver-glycogen from human samples. While mouse models are extremely useful in helping us understand certain aspects of diabetes, the ability to look directly at human samples is a crucial step if this research is to lead to new drug targets for diabetes management. This project will combine the expertise of world-leading diabetes researchers and clinicians with the skills and expertise I have helped develop at analysing glycogen structure.