Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - GLUCOTOX (Does reducing β-cell glucotoxicity increase the hyperglycaemia-lowering effect of physical exercise in type 2 diabetes?)

Teaser

While exercise may improve blood glucose control in patients with type 2 diabetes, the variability of this beneficial effect is huge and is associated with high blood glucose and poor insulin secretion. The objective of this project was to investigate the effect of high blood...

Summary

While exercise may improve blood glucose control in patients with type 2 diabetes, the variability of this beneficial effect is huge and is associated with high blood glucose and poor insulin secretion. The objective of this project was to investigate the effect of high blood glucose on exercise adaptations and to investigate the effect of muscle-derived compounds on insulin secretory function. These objectives are important to society because the findings will lead to a greater understanding of how exercise therapy may be optimised in order to maximise blood glucose control.

Work performed

The project has determined that experimental-elevation of blood glucose may impair the blood glucose control and insulin secretory function following exercise. The project also found that skeletal muscle cell secrete compounds which have a direct effect on the function of insulin secreting pancreatic beta-cells. Findings have been disseminated through departmental seminars, invited talks, and poster/oral communications at international conferences. Full manuscripts are being prepared to undergo peer-review and subsequent journal publication. Future work will be aimed at characterising the mechanistic effects muscle-derived compounds to help understand muscle to beta-cell cross talk in health and diseases like type 2 diabetes.

Final results

The project has led to the development of a novel platform for studying organ cross-talk between muscle cells and beta-cells which is beyond the state-of-the-art. This platform will continue to be used by Dr Solomon and his lab group in the future, and will allow other scientists to advance their work in the field of endocrinology. The project will have impact by advancing the scientific understanding of the mechanisms by which hyperglycaemia directly impairs metabolic and endocrine function. Further impact will be made by the identification of muscle-derived compounds which have direct functional effects on pancreatic beta-cells. These findings combined will inform the design of future studies and advance knowledge of pathophysiology of type 2 diabetes.