Niels Jessen

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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Esben Thyssen Vestergaard
  • Astrid Johanneson Hjelholt
  • Rune E Kuhre, Department of Biomedical Sciences and NNF Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • ,
  • Niels Møller
  • Pierre Larraufie, Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, UK.
  • ,
  • Fiona M Gribble, Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, UK.
  • ,
  • Frank Reimann, Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, UK.
  • ,
  • Niels Jessen
  • Jens Juul Holst, Department of Biomedical Sciences and NNF Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • ,
  • 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.

OriginalsprogEngelsk
Artikelnummerjcem_201802503
TidsskriftJournal of Clinical Endocrinology and Metabolism
Vol/bind104
Nummer7
Sider (fra-til)2581-2592
Antal sider12
ISSN0021-972X
DOI
StatusUdgivet - jul. 2019

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