The incretin hormones GIP and GLP‐1 in diabetic rats: effects on insulin secretion and small bowel motility

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 euglyce- mic and hyperglycemic conditions. Glucose-depen- dent insulinotropic peptide (10 nmol L )1 ) or GLP-1 (10 nmol L )1 ) were added to the medium and perfus- ate was collected and analysed for insulin. Moreover, GK and Wistar rats were supplied with bipolar elec- trodes 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.