The incretin hormones GIP and GLP-1 in diabetic rats: effects on insulin secretion and small bowel motility
2009 (English)In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 21, no 3, 313-321 p.Article in journal (Refereed) Published
Incretin hormones often display inhibitory actions on gut motility. The aim of this study was to investigate if altered responsiveness to glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) as regards insulin release and small bowel motility could bring further clarity to the pathophysiology of diabetes in the Goto-Kakizaki (GK) rat. The isolated perfused pancreas was studied in male GK and Wistar rats (controls) under euglycemic and hyperglycemic conditions. Glucose-dependent insulinotropic peptide (10 nmol L−1) or GLP-1 (10 nmol L−1) were added to the medium and perfusate was collected and analysed for insulin. Moreover, GK and Wistar rats were supplied with bipolar electrodes in the small bowel and myoelectric activity was recorded during intravenous administration of GIP (1–400 pmol kg−1 min−1) or GLP-1 (0.1–20 pmol kg−1 min−1). Finally, tissue was collected from GK and Wistar rats for RNA extraction. Under euglycemia, GIP and GLP-1 stimulated the initial insulin response by 10-fold in GK rats (P < 0.05). At later hyperglycemia, the insulin response to GIP and GLP-1 was blunted to about one-third compared with controls (P < 0.05). In the bowel GLP-1 was about 2.6–16.7 times more potent than GIP in abolishing the migrating myoelectric complex in the GK and control rats. Polymerase chain reaction (PCR) showed GIP and GLP-1 receptor gene expression in pancreatic islets and in small bowel. The initially high, but later low insulin responsiveness to stimulation with GIP and GLP-1 along with inhibition of small bowel motility in the GK rat indicates a preserved incretin response on motility in diabetes type 2.
Place, publisher, year, edition, pages
2009. Vol. 21, no 3, 313-321 p.
Gut Hormones, Diabetes, Motility
Gastroenterology and Hepatology
Research subject Medical Science
IdentifiersURN: urn:nbn:se:uu:diva-170774DOI: 10.1111/j.1365-2982.2008.01229.xPubMedID: 19126188OAI: oai:DiVA.org:uu-170774DiVA: diva2:509470