# Alpha- to Beta-Cell Communication in Health and Disease

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $567,643

## Abstract

Summary of Work
Glucagon is canonically viewed as an essential counterregulatory hormone that prevents hypoglycemia by driving
endogenous glucose production (EGP) in the liver. We and others have revealed additional roles for glucagon
that emphasize a much more complex control of metabolism beyond hypoglycemia. On such role is our studies
revealing the potent insulinotropic actions of glucagon in β-cells, which we have shown to be essential for
postprandial glucose control. Glucagon production in α-cells comes from the specific processing of a proglucagon
peptide by prohormone convertase 2 (PC2). Emerging literature has proposed that α-cells can differentially
process the proglucagon hormone to produce glucagon-like peptide 1 (GLP-1) through a distinct prohoromone
convertase; PC1. GLP-1 is a much more potent insulinotropic peptide, which would enhance α- to β-cell
communication and insulin secretion to a greater extent than glucagon. Our work in human subjects has
suggested that α- to β-cell communication becomes greater contributor to insulin secretion with increase
metabolic stress, raising the hypothesis that mechanisms that enhance this axis may do so a compensatory
mechanism to enhance insulin secretion in the setting of increase peripheral insulin resistance that associates
with obesity and/or type 2 diabetes (T2D). We have generated several mouse models that support this hypothesis
with strong preliminary data and propose here to move this hypothesis into a translational setting. We will utilize
preclinical studies in human islets as well as clinical studies in human subjects to test the importance of α- to β-
cell communication for insulin secretion across the metabolic spectrum and enhance our understanding of how
α-cells process proglucagon peptides to support β-cell function. This work has direct implications in the
understanding of the pathogenesis of T2D as well as the mechanisms by which incretin-based drugs control
glucose homeostasis.

## Key facts

- **NIH application ID:** 11073250
- **Project number:** 1R01DK142423-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Jonathan E Campbell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $567,643
- **Award type:** 1
- **Project period:** 2024-09-20 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11073250

## Citation

> US National Institutes of Health, RePORTER application 11073250, Alpha- to Beta-Cell Communication in Health and Disease (1R01DK142423-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11073250. Licensed CC0.

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