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

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

doi:10.1210/jc.2018-02503

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

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

Endocrinology and Metabolism

5 Citations (Scopus)

Abstract

Glucagon-like peptide-1 (GLP-1) is an incretin hormone used therapeutically in type 2 diabetes and obesity. The interplay between ambient free fatty acids (FFAs) and GLP-1 remains unclear. Acipimox suppresses adipose tissue lipolysis via activation of the PUMA-G (also known as HCA2 and GPR109a) receptor. Objective: To investigate whether 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 intra-arterially and intraluminally, and L-cells 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 before an oral glucose test. The hypopituitary patients received acipimox 250 mg 12, 9, and 2 hours before and during the metabolic study day, when they were studied in the basal state and during a hyperinsulinemic euglycemic clamp.

Original language	English
Journal	The Journal of clinical endocrinology and metabolism
Volume	104
Issue number	7
Pages (from-to)	2581-2592
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2018-02503
Publication status	Published - 21 Mar 2019

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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. The Journal of clinical endocrinology and metabolism, 104(7), 2581-2592. https://doi.org/10.1210/jc.2018-02503

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abstract = "Glucagon-like peptide-1 (GLP-1) is an incretin hormone used therapeutically in type 2 diabetes and obesity. The interplay between ambient free fatty acids (FFAs) and GLP-1 remains unclear. Acipimox suppresses adipose tissue lipolysis via activation of the PUMA-G (also known as HCA2 and GPR109a) receptor. Objective: To investigate whether 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 intra-arterially and intraluminally, and L-cells 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 before an oral glucose test. The hypopituitary patients received acipimox 250 mg 12, 9, and 2 hours before and during the metabolic study day, when they were studied in the basal state and during a hyperinsulinemic euglycemic clamp.",

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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

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N2 - Glucagon-like peptide-1 (GLP-1) is an incretin hormone used therapeutically in type 2 diabetes and obesity. The interplay between ambient free fatty acids (FFAs) and GLP-1 remains unclear. Acipimox suppresses adipose tissue lipolysis via activation of the PUMA-G (also known as HCA2 and GPR109a) receptor. Objective: To investigate whether 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 intra-arterially and intraluminally, and L-cells 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 before an oral glucose test. The hypopituitary patients received acipimox 250 mg 12, 9, and 2 hours before and during the metabolic study day, when they were studied in the basal state and during a hyperinsulinemic euglycemic clamp.

AB - Glucagon-like peptide-1 (GLP-1) is an incretin hormone used therapeutically in type 2 diabetes and obesity. The interplay between ambient free fatty acids (FFAs) and GLP-1 remains unclear. Acipimox suppresses adipose tissue lipolysis via activation of the PUMA-G (also known as HCA2 and GPR109a) receptor. Objective: To investigate whether 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 intra-arterially and intraluminally, and L-cells 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 before an oral glucose test. The hypopituitary patients received acipimox 250 mg 12, 9, and 2 hours before and during the metabolic study day, when they were studied in the basal state and during a hyperinsulinemic euglycemic clamp.

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M3 - Journal article

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SN - 0021-972X

VL - 104

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EP - 2592

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 7

ER -

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

Abstract

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