Metabolically phenotyped pancreatectomized patients as living donors for the study of islets in health and diabetes

Abstract

BackgroundThe availability of human pancreatic islets with characteristics closely resembling those present in vivo is instrumental for ex vivo studies in diabetes research.Scope of reviewIn this review we propose metabolically phenotyped surgical patients as a novel source of pancreatic tissue for islet research. Laser Capture Microdissection from snap frozen surgical specimens is a relatively simple, reproducible and scalable method to isolate islets of highest purity for many types of “omics” analyses. Fresh pancreatic tissue slices enable the functional characterization of living islet cells in situ through dynamic experiments. Access to complete medical history and laboratory values for each donor offers the opportunity of direct correlations with different “omics” data and detailed metabolic profiling prior to pancreas surgery. Peripheral blood samples complete the picture of each patient and represent a platform for pursuit of biomarkers with uniquely comprehensive background information in regard to the donor's islet cells.Major conclusionsLiving donors provide the scientific community with a steady and abundant supply of excellent material to study islets closest to their in situ environment, thus advancing our understanding of their physiology in health and diseases.

Molecular and functional profiling of human islets: from heterogeneity to human phenotypes

“…Notwithstanding the potential impacts of the pancreatic tumours being resected on metabolic phenotypes, this approach has allowed the direct linking of islet transcript profiles and expression quantitative trait loci (eQTL) with impaired glucose tolerance and type 2 diabetes in patients [39] and may address some of the quality concerns inherent to the study of islets isolated from pancreases of organ donors, such as the potential impact of prolonged ischaemic times or hospital stays [38]. This approach is now suggested as a source of living donor tissue and live-islet assessment [40] which would allow direct correlations spanning from cell physiology, to molecular genetic and genomic profiling, to in vivo human phenotypes. Although many patient samples (>100) have been assessed for molecular profiling using lasercaptured islets from fixed pancreas samples, it remains to be determined how efficiently this can be adapted to the in vitro assessment of live islets.…”

TIGER: The gene expression regulatory variation landscape of human pancreatic islets

“…The islets of Langerhans, which are clusters of specialized endocrine cells that are essential to maintain glucose homeostasis, play a central role in the etiology of T2D ( Eizirik et al, 2020 ; Krentz and Gloyn, 2020 ). Because human islets are difficult to obtain ( Barovic et al, 2019 ; Burgarella et al, 2013 ; Meier et al, 2015 ), large multi-tissue resources such as GTEx do not contain islet data and at best use whole pancreas as a proxy, despite the fact that 97% of the pancreatic tissue consists of exocrine cells that mask islet signals. Hence, the development of publicly available resources and tools that include data on islets is essential to translate T2D genetic signals into molecular and physiological mechanisms.…”

Schutz und Regeneration der Betazellen

“…Um Einblicke in die Mechanismen zu gewinnen, die für das Fortschreiten der Betazelldysfunktion bei Typ-2-Diabetes (T2D) verantwortlich sind, baut das DZD die "Human Islet Biobank" auf. Darin werden pankreatisches Gewebe und Blutproben von metabolisch charakterisierten Patienten gesammelt, die einer kompletten oder teilweisen Pankreatektomie unterzogen wurden [1]. Die in der Biobank gesammelten Proben werden in verschiedenen Forschungsprojekten verwendet um neue Erkenntnisse insbesondere der Pathogenese von Typ-2-Diabetes zu gewinnen.…”