Using a combination of two genomic methods, researchers have shown that pancreatic exocrine cells are involved in type 1 diabetes.
Researchers at the University of California at San Diego, USA, have identified a predictive causal role for certain cell types in type 1 diabetes by mapping their genetic basis.
According to the researchers, type 1 diabetes is characterized by the impairment and loss of insulin-producing pancreatic beta cells and the subsequent hyperglycemia. The mechanisms of type 1 diabetes, including the triggering of autoimmunity, are poorly understood. Because of its strong genetic component, numerous genome-wide association studies (GWAS) have been conducted in recent years, in which researchers compare entire genomes of people with the same disease or condition. In the case of type 1 diabetes, identified risk variants were largely found in the non-coding regions of the genome.
In the new study, the team integrated GWAS data into epigenomic maps of cell types in peripheral blood and in the pancreas. Epigenomic mapping describes how and when genes in cells are switched on and off and thus determines the production of proteins that are important for certain cell functions.
In particular, the researchers conducted the largest GWAS to date for type 1 diabetes, analyzing 520,580 genome samples to identify 69 new association signals. They then mapped 448,142 cis-regulatory elements (non-coding DNA sequences in or near a gene) in pancreatic and peripheral blood cell types.
“By combining these two methods, we were able to identify cell-type-specific functions of disease variants and discover a predictive causal role for pancreatic exocrine cells in type 1 diabetes, which we were able to validate experimentally,” said lead author, Assistant Professor Kyle Gaulton.
The team says pancreatic exocrine cells produce enzymes that are secreted into the small intestine, where they help digest food.
“The implication is that the dysfunction of exocrine cells can make a significant contribution to the disease. This study provides a genetic roadmap that we can use to determine which exocrine genes may play a role in disease pathogenesis, ”said co-author Professor Maike Sander.
The results will be published in Nature.