| 1. |
- Ehrström, M, et al.
(författare)
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Pharmacokinetic profile of orexin A and effects on plasma insulin and glucagon in the rat
- 2004
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 119:3, s. 209-212
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Tidskriftsartikel (refereegranskat)abstract
- Orexin A (OXA) is found in the central nervous system (CNS) and in the gut. Peripheral administration of OXA to rats results in an inhibition of fasting motility. Plasma OXA increases during fasting and central administration of OXA increases food intake. The aim of the present study was to assess the pharmacokinetic profile of OXA and the effect of intravenously (IV) administered OXA on plasma concentrations of insulin and glucagon concentrations. Rats were given OXA IV (100 pmol kg-1 min-1) for time periods of 0, 10, 20, 30 min and for 10, 20, 30 min after ceasing a 30-min infusion. After each time period, rats were then sacrificed and blood obtained. OXA was also administered at increasing doses (0, 100, 300 and 500 pmol kg-1 min-1) for 30 min and blood was obtained. Plasma OXA, insulin and glucagon levels were measured using commercially available radioimmunoassay (RIA) kits. The plasma half-life of OXA was 27.1±9.5 min. Stepwise increasing infusion rates of OXA confirmed a linear concentration-time curve and thus first-order kinetics. Its volume of distribution indicated no binding to peripheral tissues. Plasma glucagon decreased during infusion of OXA, while insulin was unaffected. Plasma OXA was raised fourfold after food intake. Thus, OXA has a longer plasma half-life than many other peptides found in the gut. This needs to be taken into account when assessing effects of OXA on biological parameters after peripheral administration.reserved.
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| 2. |
- Hellström, P. M., et al.
(författare)
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GLP-1 suppresses gastrointestinal motility and inhibits the migrating motor complex in healthy subjects and patients with irritable bowel syndrome
- 2008
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 20:6, s. 649-659
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide-1 (GLP-1) is released after food intake to act as an incretin. GLP-1 also inhibits gastric emptying and increases satiety. In rats, GLP-1 inhibits small bowel motility. Our aim was to study the effects of GLP-1 on gastrointestinal motility in healthy subjects and patients with irritable bowel syndrome (IBS). Antro-duodeno-jejunal manometry was carried out during a 4-h control period with saline, followed by a 4-h period with intravenous GLP-1 (healthy: 0.7 and 1.2 pmol kg-1 min-1 (n = 16), IBS, 1.2 and 2.5 pmol kg-1 min-1 (n = 14). Plasma was analysed for GLP-1 and gut hormones, and gut tissue expression of GLP-1 receptor was studied. In healthy subjects, GLP-1 0.7 pmol kg-1 min-1 reduced the migrating motor complexes (MMCs) from a median of 2 (range 2-3) to 0.5 (0-2), and motility index from 4.9 ± 0.1 to 4.3 ± 0.3 ln ∑(mmHg*s min-1) in jejunum, while GLP-1 1.2 pmol kg -1 min-1 diminshed MMCs from 2 (2-3) to 1.5 (1-2.5), and motility index from 5.2 ± 0.2 to 4.4 ± 0.2. In IBS patients, GLP-1 1.2 pmol kg-1 min-1 reduced the MMCs from 2.5 (2-3.5) to 1 (0-1.5) without affecting motility index. At 2.5 pmol kg-1 min -1 GLP-1 decreased MMCs from 2 (1.5-3) to 1 (0.5-1.5), and motility index from 5.2 ± 0.2 to 4.0 ± 0.5. Motility responses to GLP-1 were similar in antrum and duodenum. Presence of the GLP-1 receptor in the gut was verified by reverse transcriptase PCR. In conclusion, the gut peptide GLP-1 decreases motility in the antro-duodeno-jejunal region and inhibits the MMC in healthy subjects and IBS patients. © 2008 The Authors.
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| 3. |
- Schmidt, P.T., et al.
(författare)
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Circulating ghrelin levels after food intake during different phases of the migrating motor complex in man.
- 2006
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 36:7, s. 503-509
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Tidskriftsartikel (refereegranskat)abstract
- Background The timing of the migrating motor complexes (MMC) at food intake may influence gastric emptying and release of regulatory hormones. This report studies the relationships between phases I (motor quiescence) and II (intermediate frequency contractions) of MMC and prandial gut hormone response. Materials and methods Seven fasting volunteers ingested a meal during phase I or II of MMC verified by manometry, using paracetamol as a marker for gastric emptying. Blood was sampled before, during and 210 min after food intake for analysis of ghrelin, motilin, insulin and paracetamol. Results The basal level of ghrelin during phase I was 127·5 ± 25·4 pmol L-1 and during phase II was 132·4 ± 24·8 pmol L-1. After food intake during phase I, ghrelin fell to 77·2 ± 10 pmol L-1; in phase II it fell to 82·7 ± 17·8 pmol L-1 within 60 min and returned to baseline levels after 120 min. Baseline levels of motilin were 16 ± 2 pmol L-1 and 18 ± 3 pmol L-1 during phases I and II, respectively. After food, motilin decreased to 8·5 ± 0·7 pmol L-1 and 8·7 ± 1·0 pmol L-1 within 60 min and returned to baseline after 90 min. Insulin levels in phases I and II were 8·1 ± 1·2 mU L-1 and 8·6 ± 0·7 mU L-1, respectively, reaching 138·9 ± 35·6 mU L-1 and 167·4 ± 30·0 mU L-1 at 45 min postprandially. Conclusions The nutritional status of the gastrointestinal tract at food intake had only a limited impact on plasma ghrelin. After food intake, plasma ghrelin drops, similar to motilin, and resumes preprandial levels within 120 min.
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