# Modeling diabetes using an integrated plate system

> **NIH NIH UH3** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $2,261,232

## Abstract

Summary: Modeling Diabetes in an Integrated Plate System
The control of nutrient homeostasis involves the cross talk between multiple organ systems including the
gastrointestinal tract, liver, endocrine pancreas, and nervous system, among others. Eating, digestion and
nutrient absorption trigger a number of downstream effects on the liver and pancreas that are mediated by
nutrients and GI hormones. Type 2 diabetes (T2D) is a metabolic disease that involves all of these organ
systems. The most effective cure for T2D is gastric bypass surgery, which is invasive and has complications,
but results in improved beta cell function and reversal of insulin resistance in the liver. It is not known why
surgery is curative, however the changes in GI hormones that accompany this reversal of T2D are believed to
contribute. Current efforts to study the interplay between liver, pancreas and the GI tract have depended on
animal models, which often do not recapitulate human physiology. Moreover due to the inter-organ effects of
systemic factors like hormones and nutrients, it is challenging to separate direct vs indirect effects on organ
systems in vivo. This proposal aims to develop a tractable, high throughput fluidic system containing human
pluripotent stem cell (PSC)-derived liver, pancreas and intestine to study inter-organ crosstalk, to identify
mechanisms involved in reversal of T2D, and to develop a high throughput-screening platform for basic
research and therapeutic screening purposes.
Aim 1: Develop integrated plate systems that can support organoid function and communication.
Manufacture and deliver 36PillarPlate system (UG3) 384PillarPlate (UH3) systems.
Aim 2: Synthesize tunable hydrogels for robust and reproducible organoid growth and function. Identify
biomimetic hydrogels that support the short-term growth of liver, intestinal and pancreatic tissues (UG3) and
support organoid function and growth for 4 weeks (UH3).
Aim 3: Establish liver, intestine, and pancreas organoids in the integrated plate system.
Incorporate and test individual organoid systems for function on 36PillarPlate (UG3) 384-well micropillar
platform (UH3). Test for organ function and crosstalk for up to 4 weeks.
Aim 4: Validate the integrated plate system with known therapeutics for T2D (UH3 only).

## Key facts

- **NIH application ID:** 10216388
- **Project number:** 4UH3DK119982-03
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** MOO-YEAL LEE
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,261,232
- **Award type:** 4N
- **Project period:** 2018-09-20 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216388

## Citation

> US National Institutes of Health, RePORTER application 10216388, Modeling diabetes using an integrated plate system (4UH3DK119982-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10216388. Licensed CC0.

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