Unlocking the Secrets of Diabetes with Human Pancreatic Islets
In the global race to understand, treat, and ultimately cure diabetes, scientists face a paradoxical challenge: the very cells that hold the key to unraveling the disease's mysteries are exceptionally difficult to obtain. Pancreatic islets—tiny clusters of hormone-producing cells scattered throughout the pancreas—are the body's master regulators of blood sugar. Within these microscopic structures, beta cells produce insulin, the hormone deficient in diabetes.
For decades, researchers have relied on animal models, but critical differences in biology mean that findings in rodents often don't translate to humans. The supply of human islets for research has long been a major bottleneck, limiting the pace of discovery and keeping potential breakthroughs just out of reach.
Enter The IsletCore Program, a pioneering initiative based at the University of Alberta that has transformed the landscape of diabetes research. Established in 2010, this facility has addressed the critical shortage of human pancreatic islets by creating a systematic pipeline for their isolation, quality assessment, and distribution to scientists worldwide 1 . In this article, we'll explore how a program founded on the principles of collaboration and resource optimization has successfully satisfied the growing demand for these precious research materials, enabling discoveries that are shedding new light on one of humanity's most pervasive chronic diseases.
While animal models have contributed significantly to our understanding of basic pancreatic function, they fall short in capturing the nuances of human biology. Structural differences, variations in gene expression, and divergent signaling pathways all limit the translatability of animal studies to human diabetes treatments.
The importance of human islets for research is reflected in their ever-increasing demand. These precious tissues are used in diverse studies from genomic research to drug discovery and transplantation protocols.
Produce insulin
Release glucagon
Secrete somatostatin
This expanding demand has created a significant supply challenge, with the European Consortium for Islet Transplantation reporting a growing gap between human research islet supply and demand 2 . Before programs like IsletCore emerged, this scarcity threatened to stall progress in diabetes research at a time when diabetes rates were climbing globally.
The Alberta Diabetes Institute (ADI) IsletCore was established with a clear mission: to isolate, bank, and distribute human pancreatic islets and associated tissues exclusively for research purposes. Located at the University of Alberta in Edmonton, Canada, this program has grown to become one of the world's largest facilities dedicated to providing research-quality islets, serving over 170 research groups across North America, Europe, and Asia.
The program operates on a simple but powerful principle: maximizing the research potential of pancreatic tissue that would otherwise go unused. When pancreata from deceased organ donors are deemed not ideal for clinical transplantation—whether due to logistical issues, donor characteristics, or other factors—they may be offered to IsletCore instead. With proper consent from donors' families, these organs are channeled into the research pipeline rather than being discarded.
Serving over 170 research groups across North America, Europe, and Asia
Following research consent, pancreata are transported to the IsletCore facility in specialized organ preservation solutions on ice.
The pancreatic duct is carefully perfused with a blend of collagenase and protease enzymes that help break down the connective tissue.
The pancreas is placed in an automated Ricordi chamber, where gentle agitation helps liberate the islets from the surrounding tissue.
The resulting tissue mixture undergoes density gradient centrifugation, which separates the buoyant islets from the denser exocrine tissue.
The purified islets are stained with dithizone (DTZ), a zinc-binding dye that selectively stains insulin-containing beta cells red.
Throughout this process, the IsletCore team prioritizes islet purity over total yield—a deliberate choice that distinguishes research-focused isolations from those intended for clinical transplantation, where larger quantities are paramount.
One of the most practical challenges in distributing research islets lies in the logistics of shipment. Since many recipient laboratories cannot accept deliveries on weekends, IsletCore often needs to culture islets for extended periods—up to five days—before shipping. This raised a crucial question: does this extended culture time negatively impact islet yield and function? A comprehensive study conducted at IsletCore sought to answer this question by systematically examining islet outcomes during culture.
Researchers analyzed data from 197 research-specific islet isolations performed between September 2016 and January 2023. For each isolation, they meticulously documented islet equivalents (IEQ), islet particle number (IPN), islet purity, and islet function through glucose-stimulated insulin secretion tests.
| Parameter | Pre-Culture (Median) | Post-Culture (Median) | Change |
|---|---|---|---|
| Islet Equivalents (IEQ) | 252,876 | 75% of initial | 25% loss |
| Islet Purity | 85% | Not significantly changed | Stable |
| Stimulation Index | Measured | Not significantly changed | Stable |
Perhaps the most surprising finding was that most islet loss occurred within the first 24 hours of culture, with no significant additional loss with extended culture up to 136 hours (approximately 5.5 days). This discovery was operationally important—it meant that scheduling shipments to avoid weekends did not come with a substantial tissue cost.
The research also uncovered evidence of islet fragmentation—larger islets breaking down into smaller particles—during culture. This was indicated by a shift toward smaller islet size categories and a change in the Islet Particle Index (a ratio of particle count to IEQ).
Most islet loss occurs within the first 24 hours of culture, with stability maintained for up to 5.5 days.
| Islet Diameter (μm) | Pre-Culture Proportion | Post-Culture Proportion | Change |
|---|---|---|---|
| 50-100 | Baseline | Increased | ↑ |
| 101-150 | Baseline | Increased | ↑ |
| 151-200 | Baseline | Decreased | ↓ |
| 201-250 | Baseline | Decreased | ↓ |
| 251-300 | Baseline | Decreased | ↓ |
| 301-350 | Baseline | Decreased | ↓ |
| >351 | Baseline | Decreased | ↓ |
These findings have helped optimize islet distribution protocols at IsletCore and similar facilities worldwide. The knowledge that islet function remains stable despite some fragmentation and early losses has given researchers greater confidence in using shipped islets for their experiments. Furthermore, understanding the timing and pattern of islet loss has informed efforts to improve culture conditions and develop better shipping methods.
The consistent isolation and assessment of high-quality human islets depends on a carefully selected array of specialized reagents and equipment. The following table details key components of the "research toolkit" used at facilities like IsletCore:
| Reagent/Material | Function | Specific Examples |
|---|---|---|
| Enzyme Blends | Digest pancreatic connective tissue to liberate islets | Liberase MTF (Roche); CIzyme Collagenase HA (VitaCyte); Collagenase Gold (VitaCyte) |
| Organ Preservation Solutions | Maintain pancreas viability during transport | University of Wisconsin (UW) solution; Histidine-Tryptophan-Ketoglutarate (HTK) solution |
| Cell Culture Media | Support islet survival during culture | CMRL 1066 supplemented with BSA, insulin-transferrin-selenium, penicillin/streptomycin |
| Staining Dyes | Visualize and identify islets | Dithizone (DTZ) - stains zinc-rich beta cells red |
| Separation Solutions | Purify islets from exocrine tissue | Lympholite; Biocoll; continuous density gradients |
| Secretagogues | Stimulate insulin secretion for function tests | Glucose solutions (2.8mM vs. 16.7mM for stimulation index) |
| Assessment Assays | Quantify insulin content and cellular integrity | Meso Scale Discovery insulin assay; PicoGreen dsDNA quantification |
This specialized toolkit enables the precise isolation, characterization, and functional assessment that makes human islet research possible. Each component has been optimized through years of experimentation to maximize islet yield, purity, and functionality.
The IsletCore Program represents a triumph of resourcefulness and collaboration in biomedical research. By creating an efficient system for procuring, processing, and distributing human pancreatic islets, it has addressed a critical bottleneck in diabetes research. The program's rigorous approach to quality assessment—including detailed studies of islet behavior in culture—has provided researchers with reliable, well-characterized tissues that yield more reproducible and meaningful results.
The COVID-19 pandemic significantly disrupted operations, with multiple temporary closures resulting in a 41% reduction in organs processed during a 19-month period. Shipping disruptions also led to longer transit times, occasionally compromising islet quality upon arrival—highlighting the fragility of the distribution network even as demand continues to grow.
Looking ahead, programs like IsletCore will play an increasingly vital role in the diabetes research ecosystem. As scientists develop more sophisticated models of diabetes—including organoids, bioartificial pancreases, and stem cell-derived islets—the need for authentic human islets as a gold standard for comparison will only increase.
Through its first decade of operation, the IsletCore Program has demonstrated that strategic resource sharing can accelerate scientific progress. By ensuring that precious pancreatic tissues reach researchers with the ideas and expertise to study them most effectively, this innovative program continues to fuel discoveries that bring us closer to a world without diabetes.