# The regulation of fasting glucose metabolism in people with and without prediabetes

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2024 · $691,844

## Abstract

The overall aim of this application is to better understand the pathogenesis of fasting hyperglycemia and its
contribution to the development of type 2 diabetes. Insulin and glucagon are the most important
glucoregulatory hormones. There is evidence that both α-cells and β-cells (which secrete glucagon and insulin,
respectively) can directly regulate (stimulate or inhibit) each other. In addition, both hormone systems alter
glucose concentrations through effects on endogenous glucose production (EGP). Through these actions,
insulin can indirectly affect glucagon secretion and vice versa. Dysfunction of these regulatory networks leads
to prediabetes and, subsequently, to type 2 diabetes. However, the relative importance of these abnormalities,
and how they interact to differentially affect fasting vs. postprandial glucose tolerance remains unknown.
There is also controversy as to whether minute to minute variation in insulin secretion can control glucagon
secretion and whether these pulse characteristics can serve as biomarkers of islet function. In this series of
experiments, we will examine how glucagon directly, and indirectly through insulin, affects glucose metabolism.
Conversely, we will examine how insulin directly, and indirectly through glucagon, alters glucose metabolism.
Subsequently, we will use our novel methodology to measure islet hormone pulse characteristics to identify
early defects in islet cell function. The proposed experiments will help elucidate the mechanisms by which
fasting hyperglycemia develops in different subtypes of prediabetes thereby providing opportunities to
individualize intervention. In addition, we will develop new methods to quantify fasting islet function and identify
new biomarkers allowing early prevention and treatment of type 2 diabetes.

## Key facts

- **NIH application ID:** 10975231
- **Project number:** 2R01DK078646-18A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Adrian Vella
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $691,844
- **Award type:** 2
- **Project period:** 2007-08-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10975231

## Citation

> US National Institutes of Health, RePORTER application 10975231, The regulation of fasting glucose metabolism in people with and without prediabetes (2R01DK078646-18A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10975231. Licensed CC0.

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