# How Human Beta Cell Heterogeneity Impacts Islet Function

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2020 · $45,520

## Abstract

PROJECT SUMMARY
Diabetes affects over 400 million people worldwide and there is still no cure. Islets of Langerhans in the pancreas
contain the insulin producing β-cell which helps maintain blood glucose homeostasis. β-cells are excitable cells
that respond to high glucose by releasing insulin. These cells coordinate their behavior through electrical activity.
Cell-cell communication occurs through gap junctions between β-cells that allow a wave of depolarization to
propagate across the islet. Despite this coordinated response to glucose, β-cells show significant functional
variability. Various subpopulations have been identified that show distinct functional characteristics and are
altered in type 2 diabetes (T2D). It is unknown how these subpopulations interact and affect multicellular islet
dynamics. My overall goal is to understand the physiological importance of β-cell heterogeneity and whether
disruptions to this heterogeneity contribute to islet decline. To accomplish this goal, I will use live cell
fluorescence microscopy of primary human islets and computational models. Computational models can
overcome limitations associated with cell lines, murine models, and human tissue. These experimental systems
are used extensively to study islet function, but there are limitations to the extent of perturbation that can be
introduced to these systems. The electrophysiology of the islet follows well-defined physical principles that lends
itself to modeling. Using well-defined mathematical principles to explain experimental data, we can make
predictions that guide future research. In this project, I will test the overall hypothesis that a large proportion
of electrically-coupled, metabolically functional β-cells are required for proper calcium dynamics of the
intact human islet. My first aim will use primary human islets, photopharmacology, and image analysis to
characterize human β-cell subpopulation activity and metabolism in intact islets from healthy and T2D individuals.
My second aim will use a computational model of human islet electrophysiology to investigate how β-cell
subpopulations contribute to islet function. The outcomes of this project will lead to a better understanding of
how each subpopulation contributes to the function of the islet and which β-cells are required for islet function.
This will be valuable for developing more targeted therapies for diabetes that help preserve specific populations
of β-cells in order to maintain islet dynamics under disease conditions. This will also help guide stem cell
differentiation protocols to create higher functioning β-cell clusters. These novel treatments will help to slow the
progression of diabetes and improve the quality of life for those living with this disease.

## Key facts

- **NIH application ID:** 10152904
- **Project number:** 1F31DK126360-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** JaeAnn Dwulet
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-09-03 → 2022-09-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152904

## Citation

> US National Institutes of Health, RePORTER application 10152904, How Human Beta Cell Heterogeneity Impacts Islet Function (1F31DK126360-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10152904. Licensed CC0.

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