Multi-omics insight into amyloidosis of islets from metabolically stratified living surgical donors

Introduction:

Type 2 Diabetes Mellitus (T2DM) and its complications affect hundreds of millions of patients worldwide, reducing quality of life and burdening healthcare systems. Although islet amyloidosis has been recognized as an associated phenomenon to the beta cell failure in the context of T2DM, exact role of islet amyloidosis to the deterioration of beta cell function in T2DM remains elusive.

Aim:

Elucidate the role of islet amyloidosis in onset and development of beta cell failure in T2DM using a multi-omics approach.

Materials and methods:

Formalin fixed paraffin embedded sections of pancreatic tissue from metabolically profiled pancreatectomized patients (PPP) were stained using Congo red and Thioflavin S to detect amyloid. Laser capture microdissected islets retrieved from the same donors have been or are being subjected to DNA sequencing, RNA sequencing and mass spectrometry for proteomics. This data will be integrated and correlated with abundant clinical information available about each individual donor.

Results and outlook:

We determined superior sensitivity of Thioflavin S staining compared to Congo red in detection of islet amyloid plaques (detected in 52% and 24% of samples, respectively). After acquisition of remaining islet proteomes, we will proceed with bioinformatic analysis and integration of high throughput data with clinical parameters of the patients. This approach will result in an unprecedented comprehensive systems biology prospective of the phenomenon of islet amyloidosis.