Fostering improved human islet research: a European perspective
KeywordsBeta cells Diabetes research Human islets
Innovative Medicines Initiative for Diabetes: improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in diabetes
Translational approaches to disease modifying therapy of type 1 diabetes: An innovative approach towards understanding and arresting Type 1 diabetes
Laser capture microdissection
Assessing risk and progression of prediabetes and type 2 diabetes to enable disease modification
Development of a systems biomedicine approach for risk identification, prevention and treatment of type 2 diabetes
Differences in key features of islets isolated from type 2 diabetic vs non-diabetic organ donors
T2D vs ND islets
Beta cell identity
Increased number of de-differentiated beta cells, which correlates with the reduction of glucose-stimulated insulin release
Insulin secretory function
Reduced insulin release in response to acute glucose challenge, associated with lower glucose oxidation
Reduced insulin granule exocytosis associated with T2D gene variants
Beta cell turnover
Increased apoptosis, endoplasmic reticulum stress and islet cell inflammation
Possible beta cell rescue
Improved insulin secretion from T2D islets after culture
Dysregulation of DNA methylation
Different transcriptome signatures
In the second part of their review, Hart and Powers underline how the characteristics of the islets used in a large proportion of the available studies are inconsistently and marginally reported, making comparisons among studies difficult and scarcely reliable . Hence, the authors propose a list of actions to be put in place, including a record of standardised information on the islets studied, to guarantee more sound and reproducible results. We endorse this request and, certainly, the ongoing discussion will help us to move towards a balance between the need for characterisation and the feasibility of this . Over the past few years, a number of projects on islet pathophysiology have been funded by the European Union, also, in some cases, with the support of the European Federation of Pharmaceutical Industries and Associations (EFPIA), JDRF and charitable trusts (such as the Leona M. and Harry B. Helmsley Charitable Trust). These projects are IMIDIA (Innovative Medicines Initiative for Diabetes: improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in diabetes, www.imidia.org), T2DSystems (Development of a systems biomedicine approach for risk identification, prevention and treatment of type 2 diabetes, www.t2dsystems.eu), RHAPSODY (Assessing risk and progression of prediabetes and type 2 diabetes to enable disease modification, www.imi-rhapsody.eu) and INNODIA (Translational approaches to disease modifying therapy of type 1 diabetes: An innovative approach towards understanding and arresting Type 1 diabetes, www.innodia.eu). The key participating islet isolating centres have been scrupulously preparing and characterising their human islet preparations (currently more than 400) according to rigorous standardised procedures. The information to be reported on the donors’ clinical characteristics and isolated islet features will be further implemented to comply with the emerging requirements [1, 13]. Importantly, the biorepositories of isolated islets generated in these projects include several well-characterised samples obtained from organ donors with type 2 diabetes, and these are being used to shed further light on the pathophysiology of islet cells in diabetes.
As reported by Hart and Powers , the vast majority of studies on human islet cells have employed islets isolated from the pancreas of organ donors. The advantages of this model include the use of transplantation-grade procedures to yield large amounts of islets that can be evaluated in terms of composition, function, survival and molecular properties under different experimental conditions. IMIDIA and RHAPSODY, on the other hand, also introduced the standardised collection and analysis of islet samples obtained following pancreatic surgery from non-diabetic people, individuals with varying degrees of glucose intolerance, and people with recent-onset diabetes or long-standing type 2 diabetes . This has allowed the study of the molecular features of islet cells yielded by laser capture microdissection (LCM) [3, 12], as well as morphometric analysis and study of islet function in fresh tissue slices . One obvious advantage of this approach is that individuals can be metabolically investigated before surgery and, if required, after recovery from the operation. In RHAPSODY, the reliability of this approach has been corroborated by comparing the transcriptome of LCM islets from two cohorts of surgical patients collected at different research sites and according to the same stringent protocols  and through the identification of the largest subset of islet expression quantitative trait loci (QTLs) to date . Standardisation of the use of this model in different centres will further contribute to the advancement of human islet research.
All authors were responsible for drafting the article and revising it critically for important intellectual content. All authors approved the version to be published.
This manuscript is based on work performed with the support of non-profit organizations and public bodies for funding of scientific research conducted within the European Union: Innovative Medicines Initiative Joint Undertaking under grant agreeement no. 155005 (IMIDIA), which received financial contributions from the European Union’s Seventh Framework Program (FP7/2007–2013) and companies belonging to the European Federation of Pharmaceutical Industries and Associations (EFPIA); Innovative Medicines Initiative 2 Joint Undertaking under grant agreements number 115881 (RHAPSODY) and number 115797 (INNODIA), which include financial contributions from European Union’s Seventh Framework Programme (FP7/2007-2013) and Horizon 2020 research and innovation programme, EFPIA, JDRF, the Leona M. and Harry B. Helmsley Charitable Trust, and the Swiss State Secretariat for Education, Research and Innovation (SERI) under contract number 16.0097; the European Union’s Horizon 2020 research and innovation programme, project T2DSystems, under grant agreement number 667191. ALG is a Wellcome Trust Senior Fellow in Basic Biomedical Science. This work was funded in Oxford by the Wellcome Trust (095101 [ALG], 200837 [ALG], 098381 [MIM], 106130 [ALG, MIM], 203141 [MIM]), Medical Research Council (MR/L020149/1 [MIM, ALG]), and NIH (U01-DK105535; U01-DK085545 [MIM, ALG]). The research was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) (ALG, MIM). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Duality of interest
AMS and WK are employees of Sanofi-Aventis. GR has received research grants from Servier and is consultant for Sun Pharmaceuticals. MIMcC has received research grants from Pfizer, Merck, NovoNordisk, Abbvie, Sanofi-Aventis, Servier, Takeda, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Janssen and Roche; is consultant for Pfizer, NovoNordisk, Zoe Global, Merck and Eli Lilly; has received honorarium from Pfizer and Merck; is share-holder of Zoe Global. The remaining authors declare that there is no duality of interest associated with this manuscript.
- 12.Solimena M, Schulte AM, Marselli L et al (2018) 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 61(3):641–657. https://doi.org/10.1007/s00125-017-4500-3 CrossRefPubMedGoogle Scholar
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