Direct effects of exendin-(9,39) and glp-1-(9,36)amide on insulin action, b-cell function, and glucose metabolism in nondiabetic subjects

Matheni Sathananthan, Luca P. Farrugia, John M. Miles, Francesca Piccinini, Chiara Dalla Man, Alan R. Zinsmeister, Claudio Cobelli, Adrian Vella

Research output: Contribution to journalArticle

Abstract

Exendin-(9,39) is a competitive antagonist of glucagon-like peptide-1 (GLP-1) at its receptor. However, it is unclear if it has direct and unique effects of its own. We tested the hypothesis that exendin-(9,39) and GLP-1-(9,36)amide have direct effects on hormone secretion and β-cell function as well as glucose metabolism in healthy subjects. Glucose containing [3-3H]glucose was infused to mimic the systemic appearance of glucose after a meal. Saline, GLP-1-(9,36)amide, or exendin-(9,39) at 30 pmol/kg/min (Ex 30) or 300 pmol/kg/min (Ex 300) were infused in random order on separate days. Integrated glucose concentrations were slightly but significantly increased by exendin-(9,39) (365 ± 43 vs. 383 ± 35 vs. 492 ± 49 vs. 337 ± 50 mmol per 6 h, saline, Ex 30, Ex 300, and GLP-1-[9,36]amide, respectively; P = 0.05). Insulin secretion did not differ among groups. However, insulin action was lowered by exendin-(9,39) (25 ± 4 vs. 20 ± 4 vs. 18 ± 3 vs. 21 ± 410-24 dL/kg[min per μU/mL]; P = 0.02), resulting in a lower disposition index (DI) during exendin-(9,39) infusion (1,118 ± 118 vs. 816 ± 83 vs. 725 ± 127 vs. 955 ± 166 10-14 dL/kg/min2 per pmol/L; P = 0.003). Endogenous glucose production and glucose disappearance did not differ significantly among groups. We conclude that exendin-(9,39), but not GLP-1-(9,36)amide, decreases insulin action and DI in healthy humans.

Original languageEnglish (US)
Pages (from-to)2752-2756
Number of pages5
JournalDiabetes
Volume62
Issue number8
DOIs
StatePublished - Jan 1 2013

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Sathananthan, M., Farrugia, L. P., Miles, J. M., Piccinini, F., Man, C. D., Zinsmeister, A. R., Cobelli, C., & Vella, A. (2013). Direct effects of exendin-(9,39) and glp-1-(9,36)amide on insulin action, b-cell function, and glucose metabolism in nondiabetic subjects. Diabetes, 62(8), 2752-2756. https://doi.org/10.2337/db13-0140