Research led by Beckman Research Institute of City of Hope shows that altered expression of the SMOC1 gene promotes a physiological change leading to higher blood sugar and decreased insulin expression and secretion in the body, as seen in type 2 diabetes.
Writing in Nature Communications, the team explained that higher expression of SMOC1 led to insulin-producing beta cells in the pancreas transforming into glucagon-producing alpha cells.
This is a phenomenon seen in people with type 2 diabetes leading to higher blood sugar levels, as glucagon acts to boost blood sugar and lower levels of insulin, which acts to reduce blood sugar.
“In healthy people, islet cells can mature in different directions—some become more like alpha cells, others like beta cells,” explained co-lead author Adolfo Garcia-Ocaña, PhD, a professor at Beckman Research Institute of City of Hope in California, in a press statement.
“In type 2 diabetes, the path only goes one way: beta cells start imitating alpha cells. This shift may explain why insulin levels drop and glucagon levels rise in people with the disease.”
Although this one-way trend of beta cells turning into alpha cells in type 2 diabetes is known about, the cell types and genes involved in this change were less clear. To investigate this further, Garcia-Ocaña and colleagues used specific techniques to look at gene expression in islet cells over time and also at how the cells are developing and changing over time. They evaluated islet samples from 26 donors; half of whom had type 2 diabetes and half did not.
The researchers identified five different groups of alpha cells and ten genes linked to the transition from beta to alpha cells. The most important gene involved in this transition appeared to be SMOC1, which was seen in beta cells in people with type 2 diabetes.
“Normally, SMOC1 is active in healthy people’s alpha cells,” explained co-lead author Geming Lu, MD, an assistant professor at City of Hope. “But we saw it start showing up in the diabetic beta cells, too. It should not have been there.”
This research is early stage, but it suggests that dysfunctional SMOC1 is a key driver of the cellular transition to type 2 diabetes and could provide a potential target for the development of future targeted therapies for the condition.
The researchers plan to continue their research and find out more about the expression and regulation of SMOC1 in type 2 diabetes, then look for potential drug candidates that could block its abnormal expression.
