Common genetic variation in GLP1R and insulin secretion in response to exogenous GLP-1 in nondiabetic subjects: a pilot study.
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.
Sathananthan
Airani
A
Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA.
Man
Chiara Dalla
CD
Micheletto
Francesco
F
Zinsmeister
Alan R
AR
Camilleri
Michael
M
Giesler
Paula D
PD
Laugen
Jeanette M
JM
Toffolo
Gianna
G
Rizza
Robert A
RA
Cobelli
Claudio
C
Vella
Adrian
A
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*
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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