The Integrated Islet Distribution Program Answers the Call for Improved Human Islet Phenotyping and Reporting of Human Islet Characteristics in Research Articles

Niland, Joyce C.; Cravens, James; Olack, Barbara; Sowinski, Janice; Evans‐Molina, Carmella

doi:10.2337/dbi19-0019

Cited by 22 publications

(19 citation statements)

References 8 publications

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“…As can be seen in Figure 6D, overexpression of constitutively active GSK3β in human islets had no effect on the mitogenic effects of harmine, 5-IT, or GNF4877. Collectively, within the well-documented variability among human islet preparations (5)(6)(7)(8)(9)(10)(11)(12)(13)29) and the limited ability to study every drug at every possible dose in every human islet preparation, the findings in Figure 6 are compatible with the possibility that GSK3α or GSK3β inhibition by GNF4877 may provide a modest contribution to the superior mitogenic potency of GNF4877 as compared with harmine. On the other hand, if this is true, this modest contribution is unlikely to explain the 10-fold-greater mitogenic potency of GNF4877 and 5-IT on human β cells observed in Figure 5, A and C. All drugs were tested in the same 10 human islet preparations, except where lower n is indicated, reflecting lack of human islet availability.…”

Section: Resultsmentioning

confidence: 59%

Pharmacologic and genetic approaches define human pancreatic β cell mitogenic targets of DYRK1A inhibitors

Ackeifi¹,

Swartz²,

Kumar³

et al. 2020

JCI Insight

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Section: Resultsmentioning

confidence: 59%

Pharmacologic and genetic approaches define human pancreatic β cell mitogenic targets of DYRK1A inhibitors

Ackeifi¹,

Swartz²,

Kumar³

et al. 2020

JCI Insight

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“…Because a somewhat different glucose step (G5.6!G16.7 vs G3!G11) is used for the perifusion-based assessment of human islets by the Human Islet Phenotyping Program (HIPP) of the IIDP 51,58 , we also evaluated insulin secretion profiles obtained with this protocol (G5.6 ! G16.7) for control and 2h recovery period conditions.…”

Section: Resultsmentioning

confidence: 99%

“…Because a somewhat different glucose step (G5.6→G16.7 vs G3→G11) is used for the perifusion-based assessment of human islets by the Human Islet Phenotyping Program (HIPP) of the IIDP 51 , 58 , we also evaluated insulin secretion profiles obtained with this protocol (G5.6 → G16.7) for control and 2-h recovery period conditions. Overall, profiles were quite similar with baselines slightly more elevated, normal first-phase responses slightly more diminished, and second-phase plateaus quite similar ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Improved equipment and analytical techniques now allow the quantitative assessment of insulin release kinetics with customizable temporal resolution and under fully controllable incoming concentrations of glucose and/or other secretagogues of interest 36 , 37 , 44 – 49 . Dynamic perifusion studies are now routinely used to assess the quality and function of islets 46 , 50 , 51 , and microfluidic chip technologies make possible even the quantitative monitoring of single islet insulin secretion with high time resolution 52 , 53 . However, various nonstandardized systems and protocols are being used including variations in (i) low- (basal) and high- (stimulating) glucose concentrations (e.g., 3 mM→11 mM, 5.6 mM→16.7 mM, 2.8 mM→28 mM, and others), (ii) exposure times to stimulating glucose (typically, 10 to 30 min), (iii) flow rates (e.g., 30 to 1,000 μl/min), (iv) oxygen concentrations (from 21% atmospheric up to 95%), (v) quantity of islets per channel, (vi) analytical methods used to quantify insulin concentrations (enzyme-linked immunosorbent assay [ELISA], radioimmunoassay, immunochemiluminometric assay, and others), (vii) measurement units used to express results (pg/IEQ/min, ng/100islets/min, mU/l, μU/ml/ngDNA, μU/ml/ngDNA, relative values compared to baseline, percent insulin content, and others), and (viii) perifusion systems utilized.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Recovery Warm-up Time Following Cold Storage on the Dynamic Glucose-stimulated Insulin Secretion of Isolated Human Islets

et al. 2020

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Standardized islet characterization assays that can provide results in a timely manner are essential for successful islet cell transplantation. A critical component of islet cell quality is β-cell function, and perifusion-based assessments of dynamic glucose-stimulated insulin secretion (GSIS) are the most informative method to assess this, as they provide the most complex in vitro evaluation of GSIS. However, protocols used vary considerably among centers and investigators as they often use different low- and high-glucose concentrations, exposure-times, flow-rates, oxygen concentrations, islet numbers, analytical methods, measurement units, and instruments, which result in different readouts and make comparisons across platforms difficult. Additionally, the conditions of islet storage and shipment prior to assessment may also affect islet function. Establishing improved standardized protocols for perifusion GSIS assays should be an integral part of the ongoing effort to increase the rigor of human islet studies. Here, we performed detailed evaluation of GSIS of human islets using a fully automated multichannel perifusion instrument following various warm-up recovery times after cold storage that corresponds to current shipping conditions (8°C). We found that recovery times shorter than 18 h (overnight) resulted in impaired insulin secretion. While the effects were relatively moderate on second-phase insulin secretion, first-phase peaks were restored only following 18-h incubation. Hence, the biphasic profile of dynamic GSIS was considerably affected when islets were not allowed to recover for a sufficient time after being maintained in cold. Accordingly, while cold storage might improve islet cell survival during shipment and prolong the length of culture, functional assessments should be performed only after allowing for at least overnight recovery at physiological temperatures.

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“…We plan to leverage new PathViewer features like multi-image views in order to create more focused stories that will provide curated knowledge to selected data. We will also continue to promote inter-program connectivity, as we have done with other pancreas-specific resources like the Human Pancreas Analysis Program (HPAP) 16 and the Integrated Islet Distribution Program (IIDP) 31 . Finally, we are cognizant of the need to communicate biomedical research beyond the academic community, and we are exploring ways to make Pancreatlas more approachable to those without domain-specific knowledge.…”

Section: Future Workmentioning

confidence: 99%

Pancreatlas™: applying an adaptable framework to map the human pancreas in health and disease

Saunders

Messmer

Kusmartseva

et al. 2020

Preprint

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Deep phenotyping of human tissues generates complex spatial information from a variety of experimental modalities, yet images are typically condensed into small, static figures for publication and contain substantial data and metadata that never become widely available to the scientific community. Because image files are usually large, data is not easily shared or transferable even amongst collaborating researchers. While comprehensive image maps are available for some organs such as the brain, most resources are limited in their ability to accommodate multiplexed imaging with any degree of user interactivity. In recognition of this unmet need, we developed an online resource called Pancreatlas™ that integrates information technology infrastructure with enterprise imaging storage and visualization solutions. Through our custom interface, users can access curated, easy-to-navigate web pages, drill down to individual images, and deeply interact with them – all online, without lengthy downloads or software installation. Images are annotated with structured metadata, enabling users to dynamically build image datasets with biological and clinical relevance. The first version of Pancreatlas (v1.1) contains over 700 unique images acquired as whole-slide scans, confocal images, and imaging mass spectrometry, and is available at http://www.pancreatlas.org. While the overall system – entitled Flexible Framework for Integrating and Navigating Data (FFIND) – was deployed as a human pancreas-specific biological imaging resource, it can be configured to meet a myriad of imaging or other modular data management needs.

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The Integrated Islet Distribution Program Answers the Call for Improved Human Islet Phenotyping and Reporting of Human Islet Characteristics in Research Articles

Cited by 22 publications

References 8 publications

Pharmacologic and genetic approaches define human pancreatic β cell mitogenic targets of DYRK1A inhibitors

Pharmacologic and genetic approaches define human pancreatic β cell mitogenic targets of DYRK1A inhibitors

The Effect of Recovery Warm-up Time Following Cold Storage on the Dynamic Glucose-stimulated Insulin Secretion of Isolated Human Islets

Pancreatlas™: applying an adaptable framework to map the human pancreas in health and disease

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