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Defective FGFR1 Signaling Disrupts Glucose Regulation: Evidence From Humans With FGFR1 Mutations
Maria I Stamou1, Crystal J Chiu1, Shreya V Jadhav1
1Reproductive Endocrine Unit and Harvard Center for Reproductive Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Journal of the Endocrine Society
|July 3, 2024
Summary
Fibroblast growth factor receptor 1 (FGFR1) variants impact glucose regulation. Impaired FGFR1 signaling may precede insulin resistance, suggesting FGFR1 as a therapeutic target for metabolic health.
Area of Science:
- Endocrinology
- Genetics
- Metabolic Health
Background:
- Fibroblast growth factor receptor 1 (FGFR1) signaling is crucial for metabolic health.
- FGFR1 inactivation causes diabetes in mice, but direct human genetic evidence is limited.
Purpose of the Study:
- To investigate the role of naturally occurring FGFR1 variants in human glucose regulation.
- To test the hypothesis that FGFR1 variants are associated with glucose dysregulation.
Main Methods:
- A recall-by-genotype study comparing individuals with rare FGFR1 variants and noncarrier controls.
- Assessment of beta-cell function and insulin sensitivity using a frequently sampled intravenous glucose tolerance test.
- Study involved 9 FGFR1 variant carriers and 27 noncarrier controls.
Main Results:
- FGFR1 variant carriers exhibited higher beta-cell function.
- Individuals with FGFR1 variants showed lower insulin sensitivity compared to controls.
- These findings indicate a link between FGFR1 signaling and insulin resistance.
Conclusions:
- Impaired FGFR1 signaling may contribute to the early stages of diabetes pathogenesis.
- The FGFR1 signaling pathway is a potential therapeutic target for improving human metabolic health.
- Genetic variations in FGFR1 offer insights into human metabolic regulation.
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