title: Common genetic variation in GLP1R and insulin secretion in response to exogenous GLP-1 in nondiabetic subjects: a pilot study.
abstract: OBJECTIVE
  Glucagon-like peptide (GLP)-1 receptor is encoded by GLP1R. The effect of genetic variation at this locus on the response to GLP-1 is unknown. This study assessed the effect of GLP1R polymorphisms on insulin secretion in response to hyperglycemia and to infused GLP-1 in nondiabetic subjects.
  
  
  METHODS
  Eighty-eight healthy individuals (aged 26.3 +/- 0.6 years, fasting glucose 4.83 +/- 0.04 mmol/l) were studied using a hyperglycemic clamp. GLP-1 was infused for the last 2 h of the study (0.75 pmol/kg/min over 121-180 min, 1.5 pmol/kg/min over 181-240 min). beta-Cell responsivity (Phi(Total)) was measured using a C-peptide minimal model. The effect of 21 tag single nucleotide polymorphisms (SNPs) in GLP1R on Phi(Total) was examined.
  
  
  RESULTS
  Two SNPs (rs6923761 and rs3765467) were nominally associated with altered beta-cell responsivity in response to GLP-1 infusion.
  
  
  CONCLUSIONS
  Variation in GLP1R may alter insulin secretion in response to exogenous GLP-1. Future studies will determine whether such variation accounts for interindividual differences in response to GLP-1-based therapy.
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Airani
authors.initials: A
authors.lastname: Sathananthan
authors.forename: Chiara Dalla
authors.initials: CD
authors.lastname: Man
authors.forename: Francesco
authors.initials: F
authors.lastname: Micheletto
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.forename: Paula D
authors.initials: PD
authors.lastname: Giesler
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: Laugen
authors.forename: Gianna
authors.initials: G
authors.lastname: Toffolo
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rizza
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
mesh_terms: D002096:C-Peptide / Q000378:metabolism; D005838:Genotype; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D000067757:Glucagon-Like Peptide-1 Receptor; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018027:Receptors, Glucagon / Q000235:genetics*
chemical_list: D002096:C-Peptide; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1
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