GLP-1 playing the role of a gut regulatory compound.
Gastric emptying is the first step in the metabolic endocrine cascade that takes place after food intake. The incretin hormones originating in the gut, particularly GLP-1, exert multiple antihyperglycaemic actions such as enhancement of glucose-dependent insulin secretion, suppression of glucagon secretion, slowing of gastric emptying with an ensuing decrease in food intake and weight loss. From extensive studies in experimental animals and humans we have found that GLP-1 also exerts a motility-inhibiting and antispasmodic effect in the gut that was verified in healthy volunteers and patients with irritable bowel syndrome (IBS). In order to further investigate the effect of GLP-1 in humans, we used the dipeptidyl peptidase-IV resistant GLP-1 analogue ROSE-010, thereby extending its biological activity. A randomized, double-blinded, prospective clinical trial was carried out in order to investigate the effect of two doses of ROSE-010 in 166 patients suffering from pain attacks of IBS. We found that injections of ROSE-010 were twice as effective as placebo in terms of total pain relief response in those affected by pain attacks due to IBS. Our results show that basal physiological research studies can be translated into clinical use. The current pharmaceutical incentive with incretin mimetics, such as GLP-1 analogues and exenatide, is an interesting development that apart from its obvious use in diabetes type 2, may also be useful in terms of gut motility-regulating effects with effects on appetite, food intake and motility disorders that may provide an opportunity to bring about new improvements in medical care.
Department of Medical Sciences, Uppsala University, Sweden. per.hellstrom@medsci.uu.se
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D000818:Animals; D004435:Eating / Q000187:drug effects; D005746:Gastric Emptying / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D012527:Satiation / Q000187:drug effects
D052216:Glucagon-Like Peptide 1