Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients
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Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients. / Vestergaard, Esben Thyssen; Hjelholt, Astrid Johanneson; Kuhre, Rune E; Møller, Niels; Larraufie, Pierre; Gribble, Fiona M; Reimann, Frank; Jessen, Niels; Holst, Jens Juul; Jørgensen, Jens Otto Lunde.
In: The Journal of clinical endocrinology and metabolism, Vol. 104, No. 7, 2019, p. 2581-2592.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients
AU - Vestergaard, Esben Thyssen
AU - Hjelholt, Astrid Johanneson
AU - Kuhre, Rune E
AU - Møller, Niels
AU - Larraufie, Pierre
AU - Gribble, Fiona M
AU - Reimann, Frank
AU - Jessen, Niels
AU - Holst, Jens Juul
AU - Jørgensen, Jens Otto Lunde
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1210/jc.2018-02503
DO - 10.1210/jc.2018-02503
M3 - Journal article
C2 - 30726969
VL - 104
SP - 2581
EP - 2592
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 7
ER -
ID: 214748692