# Investigations to Assess the Role of Glucagon Signaling in Healthspan and Aging

> **NIH NIH R00** · UNIVERSITY OF ARIZONA · 2020 · $243,953

## Abstract

As our population ages, the incidence of Type II diabetes mellitus (T2DM) continues to rise, nearly doubling from
the age of 45 to 65. T2DM is characterized by both hyperinsulinemia and hyperglucagonemia. The majority of
research in the metabolic field has focused on the hyperinsulinemia that is characteristic of this disease.
However, inhibition of glucagon action is highly effective in treating T2DM. In fact, metformin, the most prescribed
anti-diabetic drug, activates AMP Kinase (AMPK) to inhibit hepatic glucagon signaling and limit hepatic glucose
production in T2DM. Similar to the metabolic field, research focused on the accelerated aging in T2DM has
primarily examined the role of hyperinsulinemia. Interventions and genetic models which decrease insulin
signaling enhance lifespan, alter energy metabolism, and decrease age-related diseases in the mouse. Despite
the hyperglycemia of T2DM and essential role of glucagon receptor signaling in the long-term survival of the lean
aging mouse, we lack knowledge of the role glucagon plays in the accelerated aging of obesity or the slowed
aging resulting from calorie restriction (CR). The widespread use and development of new therapeutics that
inhibit glucagon signaling to treat T2DM demand studies focused on the role of glucagon signaling in healthy
aging. I propose 3 aims focused on the role of global, hepatocyte, and adipocyte glucagon signaling in metabolic
control and progression of aging in lean, obese, and calorie restricted mice. The studies proposed in this grant
will be the first that investigate the role of glucagon signaling in healthspan, assess the response to elimination
of glucagon signaling in either the adipocyte or hepatocyte, and address the potential for alternative responses
to glucagon signaling inhibition in obesity, normal weight, and calorie restriction.

## Key facts

- **NIH application ID:** 9939376
- **Project number:** 5R00AG055649-05
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** JENNIFER HELENE STERN
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,953
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939376

## Citation

> US National Institutes of Health, RePORTER application 9939376, Investigations to Assess the Role of Glucagon Signaling in Healthspan and Aging (5R00AG055649-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9939376. Licensed CC0.

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