# Glucagon and insulin act cooperatively in the regulation of prandial hepatic glycogen metabolism

> **NIH NIH K01** · DUKE UNIVERSITY · 2021 · $129,864

## Abstract

Project Summary
Glucagon and insulin are pancreatic hormones that control the glycemic response to fasting and feeding.
Canonically, glucagon is secreted in the fasted state where it stimulates hepatic glycogenolysis and
gluconeogenesis in order to raise glycemia. Conversely, insulin is secreted in response to elevated blood glucose
to stimulate glucose uptake in peripheral tissues. These canonical, opposing effects of glucagon and insulin on
the liver overlook the long understanding that amino acids in mixed nutrient feeding stimulate the islet a-cell to
secrete glucagon. Moreover, our recent work has shown the importance of glucagon-stimulated insulin secretion
to maintaining glucose tolerance. Therefore, the expected response to a physiologic mixed nutrient meal is the
co-secretion of glucagon and insulin into portal circulation. The preliminary data presented herein support the
notion that glucagon and insulin work cooperatively, not antagonistically, to control prandial glucose metabolism.
We hypothesize that glucagon and insulin co-secretion controls hepatic glucose metabolism to allow glucose to
reach the periphery before being stored in the liver. Successful completion of this project will alter our
fundamental understanding of hepatic glucose metabolism and my provide insight for novel therapeutic targets
for the treatment of metabolic disease. Importantly, completion of the proposed aims will support several new
technical and conceptual developments that will provide a foundation for a career as an independent investigator.

## Key facts

- **NIH application ID:** 10282671
- **Project number:** 1K01DK129417-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Megan Capozzi
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $129,864
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10282671

## Citation

> US National Institutes of Health, RePORTER application 10282671, Glucagon and insulin act cooperatively in the regulation of prandial hepatic glycogen metabolism (1K01DK129417-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10282671. Licensed CC0.

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