2017, December

Largest collection of islet cells reveals new diabetes genes

A collaborative study has identified a novel cluster of dysregulated genes in the pancreatic islets of patients with type 2 diabetes. The study is part of the EU-Innovative Medicine Initiative (IMI) research consortium IMIDIA.
The goal of the IMIDIA consortium, which involved 14 European academic institutions, large pharma companies and biotech firms from 2010 to 2016, was to identify novel pathways 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 study led by Prof. Michele Solimena, DZD-Speaker, was to define which genes are abnormally expressed in islets of diabetic subjects compared to islets 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. The investigators identified nineteen genes the expression of which was altered in islets of both diabetic organ donors as well as diabetic surgical patients. 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.

Original publication:
Solimena et al., Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes. Diabetologia. 2017 Nov 28. doi: 10.1007/s00125-017-4500-3.

Validation of PDX1 as transcription factor located upstream of the T2D islet signature genes. Co-immunostaining for insulin (green) and PDX1 (red) in human EndoC-βH1 cells. Nuclei are counterstained with DAPI (blue). Source: PLID