More than 35 million Americans are currently living with type 2 diabetes (T2D) and over 115 million more have prediabetes, a precursor to T2D. Diabetes cost the US an estimated $640 billion annually, which is expected to rise in the future. For most patients, managing T2D means a lifetime of medication, monitoring blood sugar, and making significant changes to their everyday lives. But what if the next breakthrough in treating T2D lies not only in controlling blood sugar, but in restoring the cells responsible for controlling it.

Our pancreas contains specialized cells called beta cells that produce insulin, a hormone that transports sugar from the bloodstream into our body’s tissues for energy. In people with T2D, beta cells gradually lose their ability to function properly. Prolonged exposure to excess sugar and fat places immense stress on the beta cells, impairing insulin production and in some instances, causing these cells to lose their identity or even die. Due to fewer beta cells functioning properly, blood sugar becomes increasingly difficult to control, leading to diagnosis of T2D.

Current treatments including metformin, insulin, and GLP-1 receptor agonists help millions of people with diabetes manage their blood sugar, however, controlling blood sugar does not mean that the underlying cellular dysfunction has been reversed. When treatment is stopped, improvements in blood sugar control do not persist. This raises an important question: Why do these cells not recover even after restoring a healthier environment?

One possible answer is a phenomenon known as “metabolic memory”, which is the persistence of biological changes caused by previous metabolic stress, even after that stress has been removed. Imagine a house that was recently flooded, you can remove the water, but the wood continues to rot, grow mold and break down. Removing the original trigger or stress does not reset the system. In the case of pancreatic beta cells, they may retain the molecular changes induced by overnutrition and metabolic stress, which influences how they recover and continue to not function properly.

This is the exact question my research attempts to answer. I study human pancreatic beta cells exposed to high levels of sugar and fat, conditions which mimic some of the metabolic stressors associated with T2D. I then return the cells to normal conditions to investigate whether they recover. By examining changes in gene expression, as well as gene regulation, I can see which biological processes respond to stress and how many of these patterns persist during recovery. 

My preliminary findings show that during exposure to high sugar and fat, genes associated with insulin secretion cellular stress become more active. After removal of these stressful conditions, these gene expression patterns do not reverse, suggesting that the effects of metabolic stress may extend beyond the period of exposure and alter the cellular recovery. With these findings and more research, I hope to investigate what is behind these molecular changes and how we can reverse these changes, to potentially reverse cellular dysfunction and open new opportunities for lasting treatment.

Diabetes research has already transformed millions of lives, but how we keep pushing the boundaries and further advancements is to stop asking how to manage the disease and begin to ask how do we cure it? With more research we can begin to move closer towards a future where restoring the biological function of these beta cells can completely reverse diabetes and give patients their normal life back.