# Targeting alpha-cell GPCRs to stimulate glucagon and counter hypoglycemia

> **NIH NIH K01** · DUKE UNIVERSITY · 2022 · $107,154

## Abstract

PROJECT SUMMARY
Hypoglycemia is a dangerous complication of exogenous insulin therapy in Type 1 Diabetes (T1D) that is treated
by exogenous glucagon secretion. However, the use of exogenous glucagon has its own side effects and can
be complicated to administer in an emergency situation. As an alternative, stimuli that lead to robust endogenous
glucagon secretion could be effective to counter severe hypoglycemia. Glucagon secretion can be stimulated by
amino acids, like alanine and arginine, as well as by glucose-dependent insulinotropic peptide (GIP).
Remarkably, we found that while alanine or GIP alone induce modest increases in glucagon secretion, the
combination of alanine and GIP synergistically increase glucagon secretion in both isolated mouse and human
islets, as well as mice in vivo. A better understanding of the physiology of this glucagon and the mechanism of
its release is needed to determine if stimulating endogenous glucagon can treat hypoglycemia in T1D. We
hypothesize that endogenous -cell stimuli, such as GIP + alanine, can counter insulin-induced hypoglycemia.
The aims of this project are designed to elucidate whether -cell stimuli can mitigate severe hypoglycemia, how
the effects of -cell stimulation are changed in T1D, and what is the mechanism that alanine stimulates the -
cell to secrete glucagon. Successful completion of this project will enhance our understanding of the -cell and
provide insight for the basis of therapeutics for hypoglycemia or insulin co-therapies. In addition, the aims will
broaden the Candidate’s technical expertise and develop conceptual understanding of -cell physiology that will
provide a foundation for a career as an independent investigator.

## Key facts

- **NIH application ID:** 10427574
- **Project number:** 1K01DK132461-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Kimberley M El
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $107,154
- **Award type:** 1
- **Project period:** 2022-09-30 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427574

## Citation

> US National Institutes of Health, RePORTER application 10427574, Targeting alpha-cell GPCRs to stimulate glucagon and counter hypoglycemia (1K01DK132461-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10427574. Licensed CC0.

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