Nutrient consumption-dependent association of a glucagon-like peptide-1 receptor gene polymorphism with insulin secretion

• Published in: Scientific reports Vol. 10; no. 1; p. 16382
• Main Authors: Nishiya, Yuki, Daimon, Makoto, Mizushiri, Satoru, Murakami, Hiroshi, Tanabe, Jutaro, Matsuhashi, Yuki, Yanagimachi, Miyuki, Tokuda, Itoyo, Sawada, Kaori, Ihara, Kazushige
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.10.2020; Nature Publishing Group
• Subjects: 692/163; 692/4017; 692/499; 692/700; Adaptor proteins; Body Mass Index; Female; Genetic factors; Genotype; Genotypes; Glucagon-Like Peptide 1 - genetics; Glucagon-Like Peptide-1 Receptor - genetics; Humanities and Social Sciences; Humans; Insulin; Insulin - metabolism; Insulin secretion; Insulin Secretion - genetics; Insulin-Secreting Cells - metabolism; Male; Middle Aged; Mitochondria; multidisciplinary; Nutrients; Nutrients - administration & dosage; Polymorphism, Single Nucleotide - genetics; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-71853-7

Since type 2 diabetes (DM) is a life-style related disease, life-style should be considered when association between genetic factors and DM are examined. However, most studies did not examine genetic associations in consideration with lifestyle. Glucagon-like peptide-1 (GLP-1) receptor (GLP1R) mediates the insulinotropic action of GLP-1 in β-cells. We here examined the association while taking into consideration of interactions between the gene polymorphism and various nutrient factors. Participants from the population-based Iwaki study of Japanese subjects held in 2014–2017 with information on nutritional intake evaluated by self-administered dietary history questionnaire, and GLP1R genotype (rs3765467: A/G), were included (n = 1,560). Although not significant, insulin secretion indices assessed by homeostasis model assessment of β-cell function (HOMA-β) in subjects with the GG genotype tended to be lower than in those with the AA+AG genotypes in most groups stratified into tertiles based on daily nutrient consumptions (high, middle, and low). Stratification also showed that the GG genotype was a significant risk for decreased insulin secretion (HOMA-β ≤ 30) even after adjustment for multiple factors (age, body mass index, alcohol consumption), but only in the highest tertiles of energy, protein and carbohydrate consumption in men [odds ratios (95% confidence interval) 3.95 (1.03–15.1), 15.83 (1.58–158.9), and 4.23 (1.10–11.2), respectively]. A polymorphism of the GLP1R gene was associated with decreased insulin secretion in a nutrient consumption-dependent manner in Japanese men, indicating an interaction between GLP1R and nutritional factors in the pathophysiology of DM.