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

Sci Rep. 2020 Oct 2;10(1):16382. doi: 10.1038/s41598-020-71853-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Mass Index
  • Female
  • Genotype
  • Glucagon-Like Peptide 1 / genetics*
  • Glucagon-Like Peptide-1 Receptor / genetics*
  • Humans
  • Insulin / metabolism
  • Insulin Secretion / genetics*
  • Insulin-Secreting Cells / metabolism
  • Male
  • Middle Aged
  • Nutrients / administration & dosage*
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Insulin
  • Glucagon-Like Peptide 1