Predictive effect of GIPR SNP rs10423928 on glucose metabolism liver fat and adiposity in prediabetic and diabetic subjects

Peptides. 2020 Mar:125:170237. doi: 10.1016/j.peptides.2019.170237. Epub 2019 Dec 23.

Abstract

The gastric inhibitory polypeptide receptor (GIPR) regulates postprandial metabolism. In this context GIPR SNP rs10423928 seems toplay an important role in modulating glucose metabolism and insulinsensitivity. However, evidence regarding thisparticular SNP is still vague. In this study, we collected baseline data from four different dietaryintervention studies. We genotyped 424 subjects with prediabetes and 73with diabetes for GIPR SNP rs10423928 and examined its impact on glucosemetabolism, insulin sensitivity and body fat accumulation. We extended previous data by showing that carriers of the A allele withprediabetes displayed increased fasting glucose (p = 0.015). Unexpectedly,A allele carriers showed lower glucose levels 2 h (p = 0.021) after anoral glucose challenge compared to T/T homozygous individuals. A allelecarriers also showed significantly higher insulin sensitivity (p < 0.001)(assessed by Cederholm Index), indicating an enhanced ß-cell response. This study points to a potential protective role for rs10423928 inglucose metabolism and insulin sensitivity in subjects with prediabetes.Further studies are necessary to confirm these results.

Keywords: Diabetes; GIPR; Glucose metabolism; Glucose-dependent insulinotropic peptide; Insulin sensitivity; Prediabetes.

MeSH terms

  • Adiposity / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Biomarkers / metabolism
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Fatty Liver / pathology*
  • Female
  • Glucose / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prediabetic State / genetics*
  • Prediabetic State / metabolism
  • Prediabetic State / pathology
  • Predictive Value of Tests
  • Receptors, Gastrointestinal Hormone / genetics*
  • Receptors, Gastrointestinal Hormone / metabolism

Substances

  • Biomarkers
  • Receptors, Gastrointestinal Hormone
  • gastric inhibitory polypeptide receptor
  • Glucose