In type 2 diabetes (T2D), pancreatic islet beta cells gradually become unable to secrete enough insulin to regulate blood glucose levels. But what are the molecular processes taking place inside these cells along the road to diabetes? Insights into such processes would have a major impact on diabetes prevention and treatment but have largely eluded scientists thus far. Thanks to a unique dataset from living donors, and innovative multi-omics analysis, an international research team led by investigators at the Paul-Langerhans-Institute Dresden (PLID), the SIB Swiss Institute of Bioinformatics and the Max-Planck-Institute (MPI) of Biochemistry has shed some light into the processes driving islet dysfunction. The results of this collaborative study, part of the IMI RHAPSODY project, are published in the journal Nature Metabolism.
A valuable resource to investigate the prediabetic-diabetic continuum
So far, the subtle molecular processes taking place along the road to diabetes eluded scientists because human pancreatic islet data usually came from deceased donors. “In contrast, this study provides the first extensive analysis on islets in situ and plasma samples from the largest cohort of in-depth metabolically profiled living donors”, says Leonore Wigger, Computational Scientist at SIB and co-first author on the study. This approach allowed to circumvent the usual shortcomings associated with data from deceased donors, which can only be characterized as diabetic or non-diabetic, but also are in a particular state of metabolic stress associated with the donor’s terminal condition, and lacking extensive clinical and laboratory information. “Multi-omics data were thus generated using state-of-the-art approaches and integrated in a fashion not previously used in studies on islet dysregulation in relation to hyperglycemia in humans.”
Mark Ibberson, Director of SIB's Computational biology group Vital-IT and co-Principal investigator of the study concludes: “The results of this study change the way that we think about how the pancreas gets damaged in T2D, and provide a unique dataset of transcriptomic and proteomic data that can be used to enable further discoveries, for instance as an addition to existing datasets.”
Wigger L, Barovic M, Brunner A-D et al. Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories toward type 2 diabetes. Nature Metabolism 2021.