Genetic variants affecting incretin sensitivity and incretin secretion

• Published in: Diabetologia Vol. 53; no. 11; pp. 2289 - 2297
• Main Authors: Müssig, K, Staiger, H, Machicao, F, Häring, H.-U, Fritsche, A
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.11.2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Animals; Apoptosis; Biological and medical sciences; Cell growth; Diabetes; Diabetes mellitus type 2; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Gastric Inhibitory Polypeptide - metabolism; Genes; Genome-Wide Association Study; Genomes; GIPR; Glucagon; Glucagon-Like Peptide 1 - metabolism; Glucagon-like peptide-1; Glucose; Glucose-dependent insulinotropic peptide; Human Physiology; Humans; Incretins - metabolism; Incretins - secretion; Insulin resistance; insulin secretion; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Internal Medicine; KCNQ1; Kinases; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Nervous system; Pancreatic beta cell; Peptides; Proteins; Review; TCF7L2; Transcription factors; WFS1; Glucose-dependent insulinotropic peptide; Glucagon-like peptide-1; Review; Diabetes mellitus type 2; Pancreatic beta cell; Insulin secretion; Endocrinopathy; Incretin; Pancreatic hormone; Glucagon; Peptides; GIPR; Peptide hormone; Glucose; Genetics; β Cell; peptide-1; Glucagon-like; Endocrine pancreas; TCF7L2; Secretion; WFS1; Diabetes mellitus; Langerhans islet; Insulin; Variant; Sensitivity; KCNQ1
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-010-1876-8

Recent genome-wide association studies identified several novel risk genes for type 2 diabetes. The majority of these type 2 diabetes risk variants confer impaired pancreatic beta cell function. Though the molecular mechanisms by which common genetic variation within these loci affects beta cell function are not completely understood, risk variants may alter glucose-stimulated insulin secretion, proinsulin conversion, and incretin signals. In humans, the incretin effect is mediated by the secretion and insulinotropic action of two peptide hormones, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. This review article aims to give an overview of the type 2 diabetes risk loci that were found to associate with incretin secretion or incretin action, paying special attention to the potential underlying mechanisms.