Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients

Research output: Contribution to journalJournal articleResearchpeer-review

Esben Thyssen Vestergaard, Astrid Johanneson Hjelholt, Rune E Kuhre, Niels Møller, Pierre Larraufie, Fiona M Gribble, Frank Reimann, Niels Jessen, Jens Juul Holst, Jens Otto Lunde Jørgensen

Context: Glucagon-like peptide-1 (GLP-1) is an incretin hormone used therapeutically in T2DM and obesity. The interplay between ambient fatty acids (FFA) and GLP-1, remains unclear. Acipimox suppresses adipose tissue lipolysis via activation of the PUMA-G (aka HCA2 and GPR109a) receptor.

Objective: To investigate if lowering of serum FFA level with acipimox affects GLP-1 secretion.

Design: Two randomized crossover studies were performed in human subjects. Rat intestine was perfused intraarterially and -luminally and L-cell were incubated with acipimox.

Participants: The participants were healthy overweight subjects and hypopituitary adult patients.

Interventions: The overweight participants received acipimox 250 mg 60 minutes prior to an oral glucose test. The hypopituitary patients received acipimox 250 mg 12, 9, and 2 h prior to and during the metabolic study day, where they were studied in the basal state and during a hyperinsulinemic euglycemic clamp.

Results: Acipimox suppressed FFA but did not affect insulin in the clinical trials. In overweight subjects, the GLP-1 increase after the OGTT (AUC, pmol/lxmin) was more than doubled [4,119±607 [Acipimox] vs. 1,973±375 [Control], P=0.004]. In hypopituitary patients, acipimox improved insulin sensitivity (mg glucose/kg/min): 4.7±0.8 [Acipimox] vs. 3.1±0.5 [Control], P=0.005, and GLP-1 concentrations increased approximately 40%. An inverse correlation between FFA and GLP-1 concentrations existed in both trials. In rat intestine, acipimox did not affect GLP-1 secretion and L-cells did not consistently express the putative receptor for acipimox.

Conclusions: Acipimox treatment enhances systemic GLP-1 levels in both obese subjects and hypopituitary patients. Our in vitro data indicate that the underlying mechanisms are indirect.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Issue number7
Pages (from-to)2581-2592
Publication statusPublished - 2019

ID: 214748692