Studying cells in the pancreas to help prevent low blood glucose in type 1 diabetes

People with type 1 diabetes (T1D) often experience episodes of low blood glucose which are unpleasant and can be dangerous if left untreated. We’re funding Dr Thomas George Hill from the University of Oxford to study a type of pancreatic islet cell, called a delta cell, which he thinks could play a role in causing low blood glucose in T1D. This could lead to new treatments to prevent low blood glucose and improve T1D management.

What are pancreatic islet cells?

The pancreas contains clusters of cells that produce hormones. These clusters are called islet of Langerhans, or islets for short. There are several different types of cells in an islet, including the insulin-making beta cells that are destroyed in T1D.

Islets also contain alpha cells that make a hormone called glucagon, which raises blood glucose. Normally, when blood glucose gets too low, glucagon is released from alpha cells to bring it back up. In T1D, glucagon isn’t released properly, which increases the risk of low blood glucose, or a ‘hypo’.

What are delta cells?

Within islets, there are other cells called delta cells that make a hormone called somatostatin. Somatostatin stops beta cells releasing insulin and alpha cells releasing glucagon. In Thomas’ previous research, he discovered that in T1D, delta cells release too much somatostatin during low blood glucose, stopping glucagon being released.

Why are Breakthrough T1D UK funding this project?

Hypos are common in people with T1D and can be fatal in some cases. Fear of hypos can lead to poor blood glucose control and increase the risk of long-term T1D complications. Despite improvements in insulin technologies, we still don’t have an effective way to prevent hypos other than islet transplants which have lots of risks. Understanding the mechanisms behind the over production of somatostatin during low blood glucose could lead to new ways to prevent hypos.

Thomas said:

“We know that excessive somatostatin secretion from the delta cells plays a major role in restricting glucagon secretion from the alpha cells in type 1 diabetic pancreatic islets at low glucose. However, the mechanism(s) underlying this hypersecretion are largely unknown. With the fantastic support from Breakthrough T1D, I will be able to identify the cellular signalling pathways (within and between islet cells) contributing to impaired somatostatin secretion in type 1 diabetes. Identifying the major culprits involved will lead to the discovery of pharmacological agents that can be co-injected together with insulin that reverse this hormone defect and prevent the risk of severe hypoglycaemia.”

What will Thomas do in this project?

In this project, Thomas will study how delta cells change in mice that develop T1D. He will do this by marking the delta cells with a florescent tag which makes them easier to study. Thomas aims to identify genes that change during the development of T1D and proteins that may cause the delta cells to release too much somatostatin.

How will this project help people with T1D?

This project could lead to the development of new treatments that could be given with insulin to stop too much somatostatin being released and prevent the risk of hypos. Restoring the body’s natural defense against hypos could help people with T1D better manage their blood glucose levels, lowering the risk of long-term T1D complications and improving quality of life.

New treatments using glucagon to prevent hypos

New treatments are already being developed that use glucagon to prevent hypos in people with T1D. Professor Michael Weiss and his team at Indiana University are developing a new mixture of insulin and glucagon to help prevent both highs and lows in blood glucose levels. Thomas’ research could pave the way for more innovative treatments like this that regulate blood glucose whilst preventing the risk of hypos.