Affiliation:
1. Mohn Research Center for Diabetes Precision Medicine, Department of Clinical Science University of Bergen Bergen Norway
2. Hybrid Technology Hub‐Centre of Excellence Faculty of Medicine University of Oslo Oslo Norway
3. Institute for Surgical Research and Department of Transplant Medicine Oslo University Hospital Oslo Norway
4. Department of Cell Biology Harvard Medical School Boston Massachusetts USA
Abstract
AbstractAimThe variation in quality between the human islet samples represents a major problem for research, especially when used as control material. The assays assessing the quality of human islets used in research are non‐standardized and limited, with many important parameters not being consistently assessed. High‐throughput studies aimed at characterizing the diversity and segregation markers among apparently functionally healthy islet preps are thus a requirement. Here, we designed a pilot study to comprehensively identify the diversity of global proteome signatures and the deviation from normal homeostasis in randomly selected human‐isolated islet samples.MethodsBy using Tandem Mass Tag 16‐plex proteomics, we focused on the recurrently observed disparity in the detected insulin abundance between the samples, used it as a segregating parameter, and analyzed the correlated changes in the proteome signature and homeostasis by pathway analysis.ResultsIn this pilot study, we showed that insulin protein abundance is a predictor of human islet homeostasis and quality. This parameter is independent of other quality predictors within their acceptable range, thus being able to further stratify islets samples of apparent good quality. Human islets with low amounts of insulin displayed changes in their metabolic and signaling profile, especially in regard to energy homeostasis and cell identity maintenance. We further showed that xenotransplantation into diabetic hosts is not expected to improve the pre‐transplantation signature, as it has a negative effect on energy balance, antioxidant activity, and islet cell identity.ConclusionsInsulin protein abundance predicts significant changes in human islet homeostasis among random samples of apparently good quality.
Funder
National Institute of General Medical Sciences
Norges Forskningsråd
Novo Nordisk Fonden
Cited by
1 articles.
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