Common genetic variation in GLP1R and insulin secretion in response to exogenous GLP-1 in nondiabetic subjects: A pilot study

Airani Sathananthan, Chiara Dalla Man, Francesco Micheletto, Alan R. Zinsmeister, Michael Camilleri, Paula D. Giesler, Jeanette M. Laugen, Gianna Toffolo, Robert A. Rizza, Claudio Cobelli, Adrian Vella

Research output: Contribution to journalArticle

72 Scopus citations

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. RESEARCH DESIGN AND 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). β-Cell responsivity (ΦTotal) was measured using a C-peptide minimal model. The effect of 21 tag single nucleotide polymorphisms (SNPs) in GLP1R on ΦTotal was examined. RESULTS - Two SNPs (rs6923761 and rs3765467) were nominally associated with altered β-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.

Original languageEnglish (US)
Pages (from-to)2074-2076
Number of pages3
JournalDiabetes care
Volume33
Issue number9
DOIs
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

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    Sathananthan, A., Dalla Man, C., Micheletto, F., Zinsmeister, A. R., Camilleri, M., Giesler, P. D., Laugen, J. M., Toffolo, G., Rizza, R. A., Cobelli, C., & Vella, A. (2010). Common genetic variation in GLP1R and insulin secretion in response to exogenous GLP-1 in nondiabetic subjects: A pilot study. Diabetes care, 33(9), 2074-2076. https://doi.org/10.2337/dc10-0200