People with type 1 diabetes face a constant, dangerous trade-off: too little insulin and blood sugar spikes toward blindness and kidney failure; too much and it crashes into seizures or death. This project shifts the spotlight from the usual suspect—the insulin-making beta-cells that the immune system destroys—to the often-overlooked alpha-cells, which survive the attack but then malfunction. In healthy people, alpha-cells release glucagon to raise blood sugar when it dips too low. In type 1 diabetes, they instead fire glucagon at the wrong times, making high blood sugar worse, and fail to respond when sugar drops repeatedly. The researcher will compare alpha-cells in lab-grown stem-cell islets—a promising transplant therapy—against those in healthy human islets, using super-resolution imaging and artificial diabetes models. If alpha-cell function can be restored or optimised, stem-cell transplants could last longer and patients would face fewer terrifying hypoglycaemic episodes. This is fundamental science on a neglected cell type; success would open the search for drugs that improve alpha-cell behaviour, potentially giving people with type 1 diabetes steadier blood sugar control and a better quality of life without constant vigilance.
View original technical description
Context Sustaining normal blood sugar levels (BSL) in the body is a result of an interplay of several cell types in the pancreas, organised in cell clumps called islets. Islet beta-cells play a key role in lowering BSL to within a tight range by releasing the hormone insulin. Type one diabetes (T1D), a condition which often starts in childhood, occurs as a result of the body’s own immune system malfunctioning and destroying the beta-cells causing a lack of insulin which pushes BSL up uncontrollably. Current therapies for T1D focus on replacing the body’s insulin with injections, which is effective but is very difficult to get right. Persistently raised BSL are associated with multiple complications, including blindness and kidney failure, and a reduced life expectancy by more than a decade. However, too much insulin causes low BSL (hypoglycaemia) which can be unpredictable and scary as it can lead to fits and death if left untreated. Low BSL is one of the key concerns raised by patients and their carers, contributing a significant emotional burden for them in their management of T1D. While insulin gets released when BSL are high, the islet alpha-cells react to low BSL by releasing the hormone glucagon. Unlike beta-cells, alpha-cells survive the immune attack in T1D, however, their function is affected. Alpha-cells in T1D show inappropriate glucagon release when BSL are high, causing BSL to rise even further, and fail to respond adequately to repeated low BSL. Therapy options and challenges Although insulin pumps and technology have improved the quality of life for people living with T1D, most want a permanent solution, free from devices and needles. Transplantation of islets created in a lab from stem cells (SC) into patients with T1D is a promising line of therapy. Currently the transplant of SC islets (SCI) has been shown to normalise BSL, although their function declines over time. Among beta-cell-related reasons for this decline, one culprit could be the failure of alpha-cells in the SCI. Studies show that alpha-cells can help the function and survival of neighbouring cells in islets via the release of glucagon, however, little is known about how well they do in SCI. Project focus Using a combination of experimental models (human islets and SCI) and cutting-edge technology (super-resolution cell imaging) coupled with novel artificially created T1D lab models, my project will address the following: How well do alpha-cells function in SCI compared to healthy human islets? Investigate how beta-cell loss affects alpha-cell function. Optimise alpha-cell function to improve SCI Rescue alpha-cell function in T1D models. Addressing these questions will deepen current knowledge on alpha-cell behaviour, especially in SCI, and open up a search for new drugs able to improve alpha-cell function in T1D and SCI longevity. Project benefits T1D research has for a long time focused on beta-cell survival and improved insulin replacement, without in-depth investigations into how alpha-cells function in health, T1D or SCI. Development of drugs aimed at improving alpha-cell function and survival could have a real impact for patients with T1D by improving BSL control and reducing the risk of low BSL, thereby leading to better outcomes and quality of life.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know