# Microfluidic Devices for Determining Dynamics of Islets of Langerhans

> **NIH NIH R01** · FLORIDA STATE UNIVERSITY · 2020 · $356,418

## Abstract

The secretory dynamics of insulin and glucagon from individual pancreatic islets of Langerhans and the roles
that these dynamics play in hepatic glucose regulation are unknown. The long-term goal of the Roper
laboratory is to decode cellular communication to enable understanding of normal biological function and
disease progression. The objective of this proposal is to identify the control mechanisms that regulate dynamic
hormone release from islets and how dynamic hormone input to the liver optimizes net hepatic glucose control
by the liver. The central hypothesis is that insulin and glucagon released from islets of Langerhans interact with
the liver to generate a feedback loop that synchronizes islet behavior, sets the phase of the insulin and
glucagon oscillations, and promotes optimal hepatic metabolism. The rationale for performing this work is that
a thorough understanding of the dynamics of glucose-regulatory hormone secretion and glucose handling by
the liver may lead to the design of therapeutic approaches that alleviate the complications associated with
diabetes and other metabolic diseases. Guided by strong preliminary data, this hypothesis will be tested by
pursuing three specific aims: 1) Determine the dynamics of glucose-regulatory hormone release from islets, 2)
Identify the dynamics of small molecule secretion from islets that shape hormonal response, and 3) Identify the
metabolic response of hepatocytes to dynamic hormonal profiles. Under the first aim, a novel approach to
measure glucagon secretion from single islets with high temporal resolution will be utilized. This method will be
incorporated with our assay for insulin release to enable hormone oscillation amplitudes, frequencies, and
phase relationships to be identified. In the second aim, γ-aminobutyric acid and glutamate secretion will be
monitored from islets simultaneously with insulin and glucagon secretion. This will enable the determination of
the roles that these small molecules play in oscillatory hormone release. In the third aim, pulsatile hormone
profiles will be delivered to hepatocytes while monitoring glucose output. This method will facilitate the
understanding of how dynamic hormone profiles control hepatic behavior. The proposed research is innovative
because the microfluidic systems and measurement approaches developed in this proposal will allow
dynamics of islet and hepatocyte behavior to be observed for the first time. These results will provide a
significant increase in the knowledge of the interplay between the pancreas and liver, which is crucial for fully
understanding the mechanism of glucose homeostasis and how it goes awry in metabolic diseases. Ultimately,
this knowledge has the potential to guide therapeutic development for reducing the problems associated with
unregulated glucose levels in type II diabetics.

## Key facts

- **NIH application ID:** 9914104
- **Project number:** 5R01DK080714-13
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Michael Gabriel Roper
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $356,418
- **Award type:** 5
- **Project period:** 2008-04-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9914104

## Citation

> US National Institutes of Health, RePORTER application 9914104, Microfluidic Devices for Determining Dynamics of Islets of Langerhans (5R01DK080714-13). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9914104. Licensed CC0.

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