# Glucagon Mediated Potentiation of Insulin Sensitivity in Glucose Metabolism

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $334,125

## Abstract

Abstract
 The sedentary and dietary life style that evolved during the last decades has been paralleled by an
unprecedented increase in the incidence of metabolic disturbances such as hypertension, dyslipidemia, obesity
and type-2 diabetes. Glucagon, the key counter-regulatory hormone opposing insulin action, is released during
periods of hypoglycemia by pancreatic alpha-cells to stimulate hepatic glucose production and restore
euglycemia. Accordingly, excessive glucagon signaling is a crucial pathophysiological component of diabetes
mellitus and these actions have been widely studied in both type 1 and 2 diabetic patients.
 Emerging evidence suggests that glucagon regulates a range of actions that may be quite desirable in
patients with the metabolic syndrome. Indeed, potential drug targets that contain glucagon agonism have
emerged as promising therapeutic candidates for obesity and diabetes. Yet, the targeted tissues and molecular
mechanisms responsible for these beneficial effects are yet unknown. The scientific hypothesis that guides this
proposal is that glucagon, via its hepatic receptors (GcgR), potentiates TORC2-dependent components of
insulin-signaling cascade, which is further potentiated by hypothalamic GcgR signaling, to prime an individual
for enhanced whole-body glucose disposal. Under our hypothesis, the counterregulatory actions of glucagon
that maintain euglycemia during fasting, also engage mechanisms to potentiate subsequent insulin action. Our
hypothesis is formulated both on our preliminary and published data demonstrating enhanced glucose
tolerance and improved insulin sensitivity during hyperinsulinemic-euglycemic clamp in mice pretreated with
glucagon, or a potent glucagon-receptor agonist. However, how glucagon regulates insulin action, and the
tissues responsible for these combined insulin/glucagon-effects remain unresolved.

## Key facts

- **NIH application ID:** 9878101
- **Project number:** 5R01DK112934-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Kirk Michael Habegger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,125
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878101

## Citation

> US National Institutes of Health, RePORTER application 9878101, Glucagon Mediated Potentiation of Insulin Sensitivity in Glucose Metabolism (5R01DK112934-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9878101. Licensed CC0.

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