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Understanding glucagon in Type 2

Project summary

KATP channel-dependent and -independent regulation of the glucagon-secreting pancreatic alpha-cell

Dr Quan Zhang will use advanced techniques to study mechanisms involved in the release of glucagon (the hormone that raises blood glucose when it falls too low) and find out how they become disrupted in diabetes.

Background to research

In people without diabetes, insulin (the hormone that lowers blood glucose when it goes too high) and glucagon (the hormone that raises blood glucose when it falls too low) ensure that glucose levels are kept within a narrow ideal range. Both Type 1 and Type 2 diabetes involve having insufficient insulin and both excess (when glucose levels are high) and insufficient (when glucose levels are low) glucagon.Glucagon is produced by alpha cells in the pancreas, but the mechanisms that control its release are still unclear. Dr Quan Zhang and his colleagues have recently shown that glucagon release is controlled by glucose metabolism, which generates energy and closes key signalling channels on the surface of alpha cells. 

Research aims

Dr Quan Zhang will study the mechanisms of glucagon release and find out how they become disrupted in diabetes. In particular, he will use mouse and human islets to consider the control of glucagon release by nutrients, hormones and existing drugs (such as sulphonylureas). He will also study interacting signals from alpha cells and their neighbouring cells, and will work to uncover new drugs that might target alpha cells. 

Potential benefit to people with diabetes

The ultimate goal of this research is to find ways of restoring normal glucagon production in people with diabetes, which could help to prevent life-threatening hypos among people treated with insulin. This work will provide important information about the mechanisms that control glucagon release and how it becomes disrupted in diabetes. This could pave the way for new diabetes therapies that specifically target glucagon release, including the use of existing drugs that could be rapidly taken up into clinical practice.

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