Researchers at JAX have found new ways to prevent and treat type 2 diabetes. They note that pancreatic cell stressors may lead to the development of the disease. Over-stimulation comes from inflammation and high blood sugar over-triggers, initiating stress responses within the cell. This stress can trigger the failure or death of insulin-producing cells in the pancreas.
The team linked the variation of some genes to an attribute of pancreatic cells in responding to stress; these genetic changes increase susceptibility to type 2 diabetes. “We hope to have new treatments by targeting these genes and stress pathways,” says Michael L. Stitzel, associate professor at JAX and leader of this research.
The current research focuses on two types of stress—ER stress and cytokine stress—in islet beta cells in the pancreas. Both of these may cause cells to fail to produce insulin or die from such insults. Thus, the researchers understood how these cells respond to stress and how genetic changes affect this response.
To achieve this, the researchers exposed human islet cells to several kinds of chemical compounds that, in turn, triggered either ER or cytokine stress. They researched changes occurring to the RNA and DNA of such cells. Through their analysis, they were surprised to identify more than 5,000 genes involved in responding to stress. Many of these genes engaged in protein synthesis, which is crucial for producing healthy insulin.
The researchers also found that stress changed about one in eight DNA regulatory regions in the cells. Many of these contained genetic variants linked to higher diabetes risk. This would suggest that in people carrying these variants, the stress response may be weaker and hence more diabetes-sensitive.
One such gene, called MAP3K5, has already been pinpointed as a player in the death of stressed islet cells. In diabetic mice carrying a mutation that leads to diabetes, higher levels of the gene cause more cell death. However, when researchers inactivated or knocked out the gene, cells were more resistant to stress.
These findings offer proof that drugs targeting MAP3K5 could avoid diabetes. Researchers identified Selonsertib, a drug currently in clinical testing for other uses, as a potential treatment. It could protect islet cells and reduce diabetes risk in individuals at high risk.
This latest research brings new hope for the prevention and treatment of Type-2 diabetes but requires further confirmation on the effectiveness of the drug.
ANI