What Happens When We Develop Type 2 Diabetes?

Despite the fact that enormous sums are invested annually in diabetes research, we are still far from being able to prevent, let alone cure, diabetes. In Denmark alone, about 350,000 people live with diabetes, and they face the daily challenge of managing their blood sugar levels.

Most diabetes patients have type 2 diabetes, and unlike type 1 patients, they still produce insulin, but their body's cells are not able to use it efficiently, and over time, they become less effective.

This large group of patients is the focus of Isabell Victoria Strandby Ernst's research. Her contribution so far consists of a completed PhD project, and she will continue her work as a postdoc in Jesper Grud Skat Madsen's research group at the Department of Biochemistry and Molecular Biology.

Focus on beta cells 

“Much of diabetes treatment focuses on managing symptoms, and although this helps, it still reduces the patient's quality of life. Therefore, researchers are looking for new ways to treat, diagnose, and potentially cure the disease. To achieve this, we need to understand what happens in the body when a patient develops diabetes. My PhD project contributes to this understanding,” she explains.

Her project centers on beta cells, whose "main purpose in life is to produce insulin to maintain stable blood sugar levels," as she describes it. These beta cells, along with other hormone-producing cells, are found in small tissue environments in the pancreas called the islets of Langerhans. A human pancreas contains 1–15 million of these islets.

When beta cells become less effective, insulin production drops, and type 2 diabetes sets in. There can be many reasons for the reduced effectiveness of beta cells, including factors like diet, ethnicity, and family history. But regardless of the underlying cause, the consequences are seen in the beta cells.

Stressed cells

“There’s a lot of research interest in beta cells for this reason. In my PhD project, I used mouse models to study which genes change in beta cells when they are exposed to metabolic stress—like when someone consumes a high-fat diet and becomes overweight. I looked at the early stages when healthy beta cells start to adapt to the onset of insulin resistance. My hypothesis is that these early-stage mechanisms can be used to develop new methods to diagnose and treat type 2 diabetes.”

The surprising finding from Isabell's mouse experiments wasn’t that the beta cells became stressed from a high-fat diet—this is expected, as beta cells are forced to work overtime to produce enough insulin.

“The surprise was that I saw signs of stressed beta cells after just one week. By ‘stressed,’ I mean inflammation. I found that genes known to be involved in inflammation and the factors regulating those genes were expressed more after just one week, and even more after three weeks. Previous studies have also seen stress in beta cells after feeding mice a high-fat diet, but it usually occurred after a longer period—like two months. I specifically wanted to look at what happens after one and three weeks, which hasn't been studied much.”

A billion people with diabetes

“Maybe the inflammation is short-lived before the beta cells switch to increased insulin production to compensate for the high-fat diet. But maybe—and this is just a thought—early inflammation could be an early marker that someone is on the way to developing type 2 diabetes.”

Isabell Victoria Strandby Ernst hopes that other researchers can build on her discovery in their further diabetes research. She is certain that more research is needed in this area:

“More and more people are developing type 2 diabetes, and it’s a trend we haven’t been able to stop. If this trend continues, by 2050, one billion people worldwide will have diabetes. The majority of these cases will be type 2 diabetes, and we still don’t have highly effective treatments.”

Data from deceased individuals

After completing her PhD, Isabell Victoria Strandby Ernst continues her diabetes research. She is now employed as a postdoc in Jesper Grud Skat Madsen's research group at the Department of Biochemistry and Molecular Biology. The group works with large amounts of patient data, aiming to extract as much knowledge as possible.

This data comes, for example, from analyses of pancreases from deceased individuals who have donated their bodies to science worldwide.

Many analyses have already been conducted, and many scientific articles have been published based on this data, but the group believes that even more knowledge can be gained. This is why Isabell Strandby Ernst and her colleagues are working to compile all the available raw data into a large pool and standardize it, so both their group and others can use it to gain new insights into type 2 diabetes.