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Published on: February 26, 2019
Genetic variants affecting incretin sensitivity and incretin secretion
K Müssig1, H Staiger, F Machicao
1Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University, 72076, Tübingen, Germany.
Diabetologia
|August 18, 2010
Summary
Genetic links to type 2 diabetes often impair pancreatic beta cell function. This review explores how type 2 diabetes risk genes impact incretin hormones, which regulate insulin secretion.
Area of Science:
- Genetics
- Endocrinology
- Metabolic Diseases
Background:
- Genome-wide association studies (GWAS) have identified numerous genetic risk factors for type 2 diabetes (T2D).
- Many T2D risk variants are associated with impaired pancreatic beta cell function.
- The precise molecular mechanisms linking genetic variations to beta cell dysfunction remain largely unclear.
Purpose of the Study:
- To review type 2 diabetes (T2D) risk loci associated with incretin secretion or action.
- To explore potential molecular mechanisms underlying these associations.
- To provide an overview of the role of incretin hormones in T2D pathogenesis.
Main Methods:
- Literature review of genome-wide association studies (GWAS) and functional studies.
- Analysis of genetic variants linked to type 2 diabetes.
- Focus on incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).
Main Results:
- Several T2D risk loci show associations with altered incretin secretion or action.
- Potential mechanisms include effects on glucose-stimulated insulin secretion, proinsulin conversion, and incretin signaling pathways.
- Genetic variations may influence the efficacy of incretin-based therapies.
Conclusions:
- Genetic factors play a significant role in modulating the incretin system in type 2 diabetes.
- Understanding these genetic links can elucidate T2D pathophysiology.
- This knowledge may inform the development of personalized therapeutic strategies for T2D.
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