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

Yuki Nishiya,Jutaro Tanabe,Miyuki Yanagimachi,Hiroshi Murakami,Kazushige Ihara,Itoyo Tokuda,Makoto Daimon,Yuki Matsuhashi,Satoru Mizushiri,Kaori Sawada

doi:10.1038/s41598-020-71853-7

Yuki Nishiya, Jutaro Tanabe + Show 8 more

Open Access

https://doi.org/10.1038/s41598-020-71853-7

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Journal: Scientific Reports	Publication Date: Oct 2, 2020
Citations: 5	License type: open-access

Affiliation: Hirosaki University

Abstract

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.

Highlights

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
Type 2 diabetes (DM), a heterogeneous disorder of glucose metabolism characterized by both insulin resistance and pancreatic β-cell dysfunction, is considered multifactorial, as many genetic and environmental factors are involved together in its pathophysiology[1,2]
We examined the effect of amounts of nutrients consumed on the association of the GLP1R polymorphism with the index of insulin secretion (HOMA-β) using groups stratified into tertiles based on daily nutrient consumptions

Summary

Introduction

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. 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. Type 2 diabetes (DM), a heterogeneous disorder of glucose metabolism characterized by both insulin resistance and pancreatic β-cell dysfunction, is considered multifactorial, as many genetic and environmental factors are involved together in its pathophysiology[1,2]. The polymorphism, rs3765467 (A/G: p.Arg131Gln), was shown to be functional with the A allele associated with a > 100% increase in GLP-1 induced insulin secretion[19] Taken together, these observations indicate that GLP1R is a DM susceptibility gene.

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