# Glucagon secretion and action in humans

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2024 · $499,634

## Abstract

The overall aim of this application is to better understand the heterogeneity in glucagon secretion and action
that we have observed in nondiabetic subjects. Abnormal glucagon secretion in the post-prandial period is
recognized to play a key role in the pathogenesis of type 2 diabetes. While glucagon’s actions on glucose
metabolism are reasonably well characterized, there is little understanding as to why individuals differ in their
hepatic responses to this hormone. More importantly, it appears that the actions of glucagon to enhance
hepatic clearance of amino acids is impaired in people with hepatic steatosis. Although there is some evidence
that glucagon stimulates lipolysis and fatty acid oxidation, a review of the literature suggests that these aspects
of glucagon’s actions have been ignored. In addition, there is no understanding as to whether the ability to
stimulate endogenous glucose production and gluconeogenesis is independent of actions on amino acid and
lipid metabolism. In rodents, α-cells mass is, in part, regulated by circulating amino acid concentrations which,
in turn stimulate glucagon secretion (increasing hepatic clearance of amino acids). Whether this liver-α-cell
axis is extant in humans is uncertain. However, our preliminary data shows that with caloric restriction fasting
glucagon decreases in concert with fasting concentrations of several amino acids. Since caloric restriction is
known to ameliorate hepatic steatosis and improve insulin action, this provides an opportunity to assess how
changes in hepatic fat content alter the response to glucagon – specifically as it applies to carbohydrate,
protein, and fat metabolism. As part of our prior work we have developed new methods to quantify glucagon
secretion in vivo so that our proposed experiments will also examine how acute changes in circulating amino
acid concentrations alter α-cell function. The experiments we propose will provide novel new information about
glucagon secretion and action in humans.

## Key facts

- **NIH application ID:** 10876895
- **Project number:** 5R01DK116231-08
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Adrian Vella
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $499,634
- **Award type:** 5
- **Project period:** 2017-09-25 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876895

## Citation

> US National Institutes of Health, RePORTER application 10876895, Glucagon secretion and action in humans (5R01DK116231-08). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10876895. Licensed CC0.

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