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Updated: Aug 8, 2026
09:31
Assessing Replication and Beta Cell Function in Adenovirally-transduced Isolated Rodent Islets
Published on: June 25, 2012
The Gain-of-Function GLP1R R131Q Variant Preserves β-Cell Function and Enhances Response to GLP-1 Receptor Agonists
Hyunsuk Lee1,2, Hannah E Christie3, Ji Seon Lee4
1Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
Diabetes Care
|August 6, 2026
Summary
The GLP1R R131Q variant preserves beta-cell function and improves glycemic control in type 2 diabetes. This genetic variation enhances response to GLP-1 receptor agonists, suggesting its potential as a pharmacogenetic marker.
Area of Science:
- Genetics and genomics
- Endocrinology
- Pharmacology
Background:
- Genetic variations in the glucagon-like peptide 1 receptor (GLP1R) influence type 2 diabetes (T2D) risk and treatment outcomes.
- The GLP1R R131Q variant was previously suggested to be protective against T2D.
Purpose of the Study:
- To investigate the functional impact of the GLP1R R131Q variant on receptor signaling, beta-cell function, and response to GLP-1 receptor agonists (GLP-1RAs).
Main Methods:
- A 20-year prospective Korean cohort (n=6,373) assessed beta-cell function using the disposition index.
- Pharmacogenetic response to GLP-1RAs was evaluated in a Korean T2D cohort (n=177).
- In vitro assays, human islet experiments, and hyperglycemic clamp studies characterized the variant's effects on receptor signaling and islet function.
Main Results:
- The GLP1R R131Q variant was linked to a slower decline in disposition index in non-diabetic individuals.
- In T2D patients, each R131Q allele significantly improved HbA1c reduction with GLP-1RA treatment.
- In vitro and human islet studies demonstrated enhanced GLP-1RA-stimulated insulin secretion and cAMP production in a dose-dependent manner.
Conclusions:
- The GLP1R R131Q variant represents a gain-of-function, preserving beta-cell function and enhancing glycemic response to GLP-1RAs.
- This variant shows promise as a pharmacogenetic marker for personalized diabetes management.
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