A combined study by Prof. Michele Solimena have demonstrated a novel cluster of dysregulated genes in the pancreatic islets of patients with type 2 diabetes. Type 2 diabetes, which affects more than 500 million people worldwide, results from the inability of beta cells in the pancreatic islets to provide the body with enough insulin to maintain blood glucose levels. These findings are now published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]).

The goal of the IMIDIA consortium, which involved 14 European academic institutions, large pharma companies and biotech firms from 02.2010 until 09.2016, was to identify novel paths for the regeneration, maintenance and protection of insulin-producing pancreatic beta cells as a mean to expedite the discovery of more effective strategies to prevent and treat diabetes.

A main task of the IMIDIA consortium was to define which genes are abnormally expressed in islet beta cells of diabetic subjects compared to islet beta cells of non-diabetic subjects. The altered expression of these genes could account for beta cell failure in diabetes. For the first time, the investigators based their comparative gene expression analysis not only on islets collected from non-diabetic and diabetic organ donors, for which the availability of clinical information is limited, but also on islets from patients undergoing pancreatic surgery.

For the latter subjects in depth medical information was available and the diabetic status could be accurately assessed immediately prior to surgery. This approach enabled therefore the assembly of the largest collection of islets from non-diabetic and diabetic subjects, but also access to islets from prediabetic individuals.  

The investigators identified in this way nineteen genes the expression of which was altered in islets of both diabetic organ donors as well as diabetic surgical patients, as compared with non-diabetic islets from these cohorts. Notably, nine of these nineteen genes had never been shown previously to be dysregulated in diabetic islets.

On the other hand, the study could not find evidence for any of these genes to be dysregulated in islets of prediabetic subjects, hence suggesting that their altered expression is a consequence rather than the cause of beta cell failure in diabetes. Hence, future studies shall be devoted to discovering which genes are dysregulated prior to the demise of the beta cells.

Prof. Michele Solimena said, "We believe that our data provides novel molecular insights into new standards for how studies in this field shall be carried out in the future. Ultimately, we are confident that our approach will provide a new view for how exposure of beta cells to nutrient overload wears their function overtime, hence impairing their ability to satisfy the excessive demand of insulin to maintain metabolic homeostasis."