Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients
Accepted author manuscript, 1.9 MB, PDF document
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 language | English |
---|---|
Journal | The Journal of clinical endocrinology and metabolism |
Volume | 104 |
Issue number | 7 |
Pages (from-to) | 2581-2592 |
ISSN | 0021-972X |
DOIs | |
Publication status | Published - 2019 |
Number of downloads are based on statistics from Google Scholar and www.ku.dk
ID: 214748692