Scientists at City of Hope have discovered a gene that plays a surprising role in the development of type 2 diabetes (T2D).
The gene, called SMOC1, seems to cause certain cells in the pancreas—normally responsible for lowering blood sugar—to start doing the opposite and raise blood sugar instead. These findings could open the door to new ways of treating, diagnosing, and possibly preventing T2D.
The study was published in Nature Communications and focused on understanding how insulin-producing cells in the pancreas disappear or stop working properly in people with diabetes. T
he pancreas contains small clusters of cells known as islets. Within these islets, beta cells produce insulin to lower blood sugar, and alpha cells produce glucagon to raise blood sugar. Keeping a healthy balance between the two hormones is key to controlling blood sugar levels.
In people with type 2 diabetes, that balance is thrown off. Some beta cells begin to lose their identity. Instead of producing insulin, they start acting like alpha cells and begin making glucagon. This leads to higher blood sugar levels and a worsening of diabetes.
To understand why this happens, scientists analyzed individual islet cells from 26 people—half had type 2 diabetes and the other half did not. They used a powerful technique called RNA sequencing to study how the cells change over time. The researchers discovered five unique types of islet cells, each with its own gene activity pattern and path of development.
In healthy people, some cells were flexible and could mature into either alpha or beta cells. But in people with diabetes, this flexibility was lost. Beta cells only transitioned into alpha cells, never the other way around. This one-way shift helps explain why insulin levels drop while glucagon levels rise in people with T2D.
The team also found something unusual—some cells, called “AB cells,” were producing both insulin and glucagon. This suggests that these cells may have the potential to become either beta or alpha cells, depending on what signals they receive. Understanding how these cells work could one day lead to new therapies that restore insulin production.
One gene stood out in the study: SMOC1. Normally, this gene is active in alpha cells. But in people with diabetes, it was active in beta cells too—and that was not good.
When SMOC1 was active in the wrong place, insulin production went down, and the beta cells started to lose their special identity and act more like alpha cells. They even showed signs of being immature or underdeveloped.
This suggests that SMOC1 may drive the transformation of healthy beta cells into alpha-like cells, contributing to the loss of insulin in people with T2D. The researchers now believe SMOC1 could be a key factor behind beta cell failure and high blood sugar.
Although SMOC1 is not well-studied in diabetes, scientists know that the protein it produces helps guide tissue growth and binds to calcium, which is important for insulin release. This means it could play an important role in both cell development and insulin function.
These discoveries offer many exciting possibilities for the future. Scientists could explore ways to stop harmful cell changes before they happen. SMOC1 might also be used as a marker to detect beta cell problems early.
Blocking SMOC1 or controlling its activity could become a new way to treat or slow down T2D. And understanding how flexible cells like AB cells work could lead to new regenerative therapies that bring back insulin production.
In upcoming studies, the City of Hope team plans to dig deeper into how SMOC1 becomes active in beta cells, what triggers it, and how to control it. They will also test new approaches to block its effects and protect healthy beta cell function.
This research gives hope that by targeting the root causes of T2D at the genetic level, new treatments may one day help millions of people better manage or even reverse their condition.
If you care about diabetes, please read studies about Vitamin D and type 2 diabetes, and to people with diabetes, some fruits are better than others.
For more health information, please see recent studies that low calorie diets may help reverse diabetes, and 5 vitamins that may prevent complication in diabetes.
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