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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acipimox | Experimental | Administration of acipimox 250 mg p.o. |
|
| Control | No Intervention | No intervention. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acipimox | Drug | P.o. administration of 250 mg acipimox |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Levels of GLP-1 in plasma | 9 months |
| Measure | Description | Time Frame |
|---|---|---|
| Lipolytic activity in adipose tissue by measuring FFA (free fatty acid) levels | 9 months | |
| Insulin sensitivity by measuring blood glucose after an OGTT | 5 months |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin secretion by measuring levels of insulin and c-peptid | 9 months | |
| Secretion of the hormones ghrelin, leptin and GIP (gastric inhibitory polypeptide) by measuring hormone levels in plasma | 9 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jens Otto L Jørgensen, Professor | University of Aarhus | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital of Aarhus | Aarhus | 8000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26885360 | 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. | |
| 26106933 | 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. |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C027696 | acipimox |
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| 12563315 | 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. |
| 24140022 | 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. |
| 1317767 | 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. |
| D004700 | Endocrine System Diseases |