LOS ANGELES: Scientists at City of Hope in the US have identified a gene that plays a crucial role in the development of type 2 diabetes, a discovery that could open new paths for treatment, diagnosis and possibly prevention of the disease.
The research, published in the journal Nature Communications, shows that a gene called SMOC1 can cause insulin-producing cells in the pancreas to malfunction and instead raise blood sugar levels.
Type 2 diabetes affects hundreds of millions of people worldwide and occurs when the body fails to use insulin properly or does not produce enough of it to regulate blood glucose.
How healthy blood sugar balance breaks down
The pancreas contains clusters of cells known as islets. Within these islets, beta cells produce insulin, which lowers blood sugar, while alpha cells produce glucagon, which raises blood sugar.
In healthy individuals, the two hormones work in balance to keep glucose levels stable.
In people with type 2 diabetes, this balance is disrupted. Some beta cells lose their identity and stop producing insulin.
Instead, they begin to behave like alpha cells and produce glucagon, worsening high blood sugar levels.
“Preserving the balance between insulin and glucagon is critical for normal blood sugar control,” City of Hope said in a statement.
Analysing human pancreatic cells
To understand why beta cells lose their function, researchers analysed individual islet cells from 26 people. Half of the donors had type 2 diabetes, while the other half did not.
Using advanced RNA sequencing techniques, the scientists examined how pancreatic cells changed over time.
They identified five distinct types of islet cells, each with its own genetic signature and developmental pathway.
In healthy individuals, some islet cells showed flexibility. They could mature into either alpha or beta cells. In people with type 2 diabetes, however, this flexibility was lost.
“In type 2 diabetes, the path only goes one way,” said Adolfo Garcia-Ocaña, lead author of the study and chair of the Department of Molecular & Cellular Endocrinology at City of Hope.
“Beta cells start imitating alpha cells. This shift may explain why insulin levels drop and glucagon levels rise in people with the disease.”
Role of the SMOC1 gene
Among the genes involved in the transition from beta cells to alpha-like cells, SMOC1 stood out as a major driver.
“Normally, SMOC1 is active in healthy people’s alpha cells,” said Geming Lu, co-corresponding author and assistant research professor at City of Hope.
“But we saw it start showing up in diabetic beta cells as well. It should not have been there.”
The misplaced activity of SMOC1 had serious consequences. Insulin production fell. Genes responsible for maintaining beta cell identity slowed down.
The affected cells showed features typical of immature or alpha cells.
Taken together, the findings suggest that SMOC1 expression in beta cells reduces insulin levels and contributes directly to rising blood sugar in people with type 2 diabetes.
Cells with dual identity
The researchers also identified a rare group of cells, called AB cells, that produce both insulin and glucagon. This finding suggests that some pancreatic cells retain the ability to switch between cell types.
“These cells may represent an opportunity for regenerative therapies,” the researchers said, noting that such flexibility could be harnessed to restore insulin production.
Although SMOC1 has not been widely studied in diabetes, scientists believe it plays an important biological role.
The protein produced by the gene binds to growth factors involved in tissue development and to calcium, which is essential for insulin release.
Based on these properties, the researchers suspect SMOC1 strongly influences the development and function of beta cells.
“Our results indicate that SMOC1 drives beta cell dysfunction and their shift toward an alpha cell-like state,” Garcia-Ocaña said.
