The Effect of Acipimox on GLP (Glucagon-like Peptide)-1 Secretion

Summary

Glucagon like peptide 1 is produced in enteroendocrine L cells in the small intestine stimulated by peroral food intake. GLP-1 induces insulin secretion, and analogues are used in the treatment of DM2 (type 2 diabetes mellitus). Recently it was found, that levels of GLP-1 are increased in response to acipimox. The hypothesis is that G protein coupled receptors on enteroendocrine L cells bind acipimox and thereby induce GLP-1 secretion. In a controlled, open, randomized experiment, eight healthy, overweight men will be studied on an intervention day, where they receive acipimox, and on a control day. The study day includes an OGTT (oral glucose tolerance test), blood samples before and after the OGTT and a biopsy from adipose tissue.

Timeline

Start

2016-06

Primary completion

2017-01-20

Completion

2017-01-20

Publications

• Background Pais R, Gribble FM, Reimann F. Stimulation of incretin secreting cells. Ther Adv Endocrinol Metab. 2016 Feb;7(1):24-42. doi: 10.1177/2042018815618177.
• Background Iepsen EW, Torekov SS, Holst JJ. Liraglutide for Type 2 diabetes and obesity: a 2015 update. Expert Rev Cardiovasc Ther. 2015;13(7):753-67. doi: 10.1586/14779072.2015.1054810.
• Background Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med. 2003 Mar;9(3):352-5. doi: 10.1038/nm824. Epub 2003 Feb 3.
• Background Newman JC, Verdin E. Ketone bodies as signaling metabolites. Trends Endocrinol Metab. 2014 Jan;25(1):42-52. doi: 10.1016/j.tem.2013.09.002. Epub 2013 Oct 18.
• Background Fulcher GR, Walker M, Catalano C, Farrer M, Alberti KG. Acute metabolic and hormonal responses to the inhibition of lipolysis in non-obese patients with non-insulin-dependent (type 2) diabetes mellitus: effects of acipimox. Clin Sci (Lond). 1992 May;82(5):565-71. doi: 10.1042/cs0820565.

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