Immature Beta Cells May Cause Type 2 Diabetes

In a new study published by Nature Communications, the investigators discovered mechanisms behind diminished insulin production among patients with type 2 diabetes.

The authors found that insulin-producing beta cells regress in their development, become immature, and cease to work. These findings may lead to novel treatments for type 2 diabetes that result from immature beta cells.

"If you can affect things at the cellular level and restore the body's own rapid regulation, you can more accurately adjust blood sugar compared to what is possible with insulin injections," said Anders Rosengren, MD, PhD.

It has been well-understood that beta cells do not work properly in type 2 diabetes, since the body is unable to produce enough insulin to control blood glucose levels, according to the study. Previous research suggests that beta cells become fewer in number, while other studies have found that the cells become dysfunctional.

The new findings are a combination of both theories. The authors discovered that beta cells become immature, which reduces the number of functional cells in the body.

Included in the study were 124 tissue samples, with 41 coming from patients with type 2 diabetes. The investigators discovered how genetic changes were able to alter the course of the disease. In the study, they likened the genetic changes to interruptions at airports.

"All airports are connected in a large network, but a disruption at a hub like Frankfurt Airport is much more serious than a disruption in Gothenburg,” Dr Rosengren said. “We searched out the hubs, ie the key genes, and the major links. Of almost 3,000 genes that were changed in diabetes, 168 could be described as Frankfurt genes. It was these we focused on.”

Upon further analysis, the authors found that the SOX5 gene affects the progression of type 2 diabetes. This finding is significant because the gene was not previously linked to diabetes, according to the study.

"If you experimentally suppress and deactivate SOX5, the function of the 168 genes deteriorate and the cells decrease in maturity. If you then increase the levels of SOX5, the 168 genes also increase and insulin delivery can be normalized," Dr Rosengren said. "It's very exciting to see. It was almost like a volume control, where you could increase or decrease the maturity level of the insulin-producing cells.

The authors hypothesize that drugs that restore the maturity of insulin-producing beta cells may not be long off. They believe that approved drugs may be able to be repurposed to mature the cells, according to the study.

The investigators also emphasize how important healthy lifestyle is for patients with type 2 diabetes. Many studies have linked SOX5 decreases to unhealthy food or low physical activity levels.

"It is important to remember that everyone is different. Some manage a long time despite unhealthy lifestyle habits. For others, the tipping point is much earlier,” Dr Rosengren concluded. “But, regardless of genetic conditions, you can do something about your disease.”