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Understanding how beta cells release insulin

Project summary

Beta cells release insulin into the blood stream, but this complex process isn’t well understood. Dr Benoit Hastoy wants to investigate the process in more detail, to try and improve the effectiveness of existing treatments for people with Type 2 diabetes.

Background to research

Beta cells in the pancreas produce insulin, which is responsible for regulating the levels of sugar in the blood. Insulin begins its life as a larger protein called proinsulin. Proinsulin is stored in small compartments inside the beta cells, before being turned into insulin and released into the bloodstream.

In people with Type 2 diabetes, these compartments appear to release their proinsulin into the bloodstream too early, before it has been turned into insulin. This is a problem because proinsulin doesn’t regulate blood sugar levels in the same way that insulin does.

Alongside this, a common treatment for Type 2 diabetes – called sulphonylureas – that trigger beta cells to release more insulin also cause the release of proinsulin, putting even more strain on the beta cells.

We don’t yet understand why beta cells in people with Type 2 diabetes release their compartment contents too early. While there are likely to be multiple reasons, Dr Hastoy believes evidence points to several different genes being involved.

Research aims

Dr Hastoy wants to understand how beta cells form their storage compartments, how they release insulin into the blood, and why this process goes wrong in people with Type 2 diabetes. He also wants to understand how changes in the genes of people with Type 2 diabetes affect the storage compartments.

Dr Hastoy will first study the storage compartments inside the beta cells, to understand how they release their contents into the bloodstream. They will then look at how mutations in different genes affect the release of the compartment contents.

Finally, Dr Hastoy will edit the genes that control insulin production, and examine how changes in insulin levels affects the compartments releasing their contents.

Potential benefit to people with diabetes

In people with Type 2 diabetes, beta cells can release insulin into the bloodstream before it’s able to do its job properly – and some Type 2 diabetes treatments encourage this as well. By understanding how and why beta cells release their contents into the bloodstream, this research could help to improve treatments and keep beta cells healthy.

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