Led by researchers at the University of Exeter, the study provided a new look at how high blood sugar changes the activity of hormone-producing cells. Its findings might enable novel therapies that restore the beta cells to their normal activity.
“Only recently, Exeter researchers discovered that people with Type 1 diabetes still retain some insulin-producing cells, but the environment produced by diabetes can be toxic for these cells that remain,” explained lead researcher Lorna Harries. “Our work could lead to new changes to protect these cells, which could help people maintain some ability to make their own insulin. (Related: Preventing and treating gestational diabetes naturally.)
Type 2 diabetes causes beta cells to transform into delta cells
In their experiment, the team simulated the conditions caused by Type 2 diabetes. They exposed human pancreatic beta cells to the diabetic environment. Both Type 1 and Type 2 diabetes caused the loss of beta cells in the pancreas. Experts theorized that the pancreatic cells died due to their inhospitable surroundings.
The new study disproved that prevailing thought. The researchers reported that some of the beta cells transformed into a different type of cell. The affected cells became delta cells. And instead of producing insulin, they started synthesizing somatostatin.
Next, the researchers examined pancreatic tissues from deceased patients with either Type 1 or Type 2 diabetes. The post-mortem evaluation showed that the pancreas of diabetic patients contained more delta cells than expected. Earlier studies using animal models showed similar results. However, the pancreatic beta cells of mice didn't transform into delta cells. Instead, they became yet another type of cell called alpha cells. Further, these cells produced glucagon, another hormone with different effects than insulin or somatostatin.
Glucagon raises glucose levels, which exacerbates the diabetic condition of the mice. Given these findings, the Exeter-led team believed that human and mice cells reacted differently to diabetes.
Diabetes disrupted RNA messages that controlled cell behavior
After learning that diabetes caused beta cells to transform into delta cells, the team investigated the reason for the changes. They examined gene regulation, the variances in the genes that selected the type of RNA message for production.
The researchers took samples of pancreatic tissues from Type 2 diabetes patients and compared them with healthy counterparts. They noticed that around a quarter of the genes in diabetic cells experienced disturbances in the standard pattern of RNA messages. RNA messages told the cells how to respond to their environment. In turn, the message type produced by the genes affected the cell's life and behavior.
Harries and her teammates theorized that variations in the regulators led to changes in the RNA messages. In turn, the altered directions might change the behavior of beta cells.
“The really exciting finding is that in the laboratory at least, we have been able to reverse the changes - turn the delta cells back to beta cells - if we restore the environment to normal, or if we treat the cells with chemicals that restore the regulator genes and the patterns of RNA messages made to normal,” explained Harries.
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