Esben Thyssen Vestergaard

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

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: Journal of Clinical Endocrinology and Metabolism, Vol. 104, No. 7, jcem_201802503, 07.2019, p. 2581-2592.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Vestergaard, ET, Hjelholt, AJ, Kuhre, RE, Møller, N, Larraufie, P, Gribble, FM, Reimann, F, Jessen, N, Holst, JJ & Jørgensen, JOL 2019, 'Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients', Journal of Clinical Endocrinology and Metabolism, vol. 104, no. 7, jcem_201802503, pp. 2581-2592. https://doi.org/10.1210/jc.2018-02503

APA

Vestergaard, E. T., Hjelholt, A. J., Kuhre, R. E., Møller, N., Larraufie, P., Gribble, F. M., Reimann, F., Jessen, N., Holst, J. J., & Jørgensen, J. O. L. (2019). Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients. Journal of Clinical Endocrinology and Metabolism, 104(7), 2581-2592. [jcem_201802503]. https://doi.org/10.1210/jc.2018-02503

CBE

Vestergaard ET, Hjelholt AJ, Kuhre RE, Møller N, Larraufie P, Gribble FM, Reimann F, Jessen N, Holst JJ, Jørgensen JOL. 2019. Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients. Journal of Clinical Endocrinology and Metabolism. 104(7):2581-2592. https://doi.org/10.1210/jc.2018-02503

MLA

Vancouver

Vestergaard ET, Hjelholt AJ, Kuhre RE, Møller N, Larraufie P, Gribble FM et al. Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients. Journal of Clinical Endocrinology and Metabolism. 2019 Jul;104(7):2581-2592. jcem_201802503. https://doi.org/10.1210/jc.2018-02503

Author

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. / Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients. In: Journal of Clinical Endocrinology and Metabolism. 2019 ; Vol. 104, No. 7. pp. 2581-2592.

Bibtex

@article{ed70f0bf309644fa9649eeb7a3c92126,
title = "Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients",
abstract = "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.",
keywords = "ADIPOSE-TISSUE, DEGRADATION, ENTEROENDOCRINE CELLS, FREE FATTY-ACID, GROWTH-HORMONE, INSULIN, METABOLISM, NICOTINIC-ACID, PLASMA-GLUCOSE, PYY SECRETION",
author = "Vestergaard, {Esben Thyssen} and Hjelholt, {Astrid Johanneson} and Kuhre, {Rune E} and Niels M{\o}ller and Pierre Larraufie and Gribble, {Fiona M} and Frank Reimann and Niels Jessen and Holst, {Jens Juul} and J{\o}rgensen, {Jens Otto Lunde}",
year = "2019",
month = jul,
doi = "10.1210/jc.2018-02503",
language = "English",
volume = "104",
pages = "2581--2592",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "7",

}

RIS

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 - 2019/7

Y1 - 2019/7

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.

KW - ADIPOSE-TISSUE

KW - DEGRADATION

KW - ENTEROENDOCRINE CELLS

KW - FREE FATTY-ACID

KW - GROWTH-HORMONE

KW - INSULIN

KW - METABOLISM

KW - NICOTINIC-ACID

KW - PLASMA-GLUCOSE

KW - PYY SECRETION

UR - http://www.scopus.com/inward/record.url?scp=85066352100&partnerID=8YFLogxK

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

M1 - jcem_201802503

ER -