Andreas Lindqvist, Mikael Ekelund, Stefan Pierzynowski, Leif Groop, Jan Hedenbro and Nils Wierup
Background: In most patients gastric bypass (GBP) causes remission of type 2 diabetes. It is established that plasma levels of gut hormones are affected by GBP, but it is not well understood how the enteroendocrine cells producing these gut hormones are affected by GBP. Objectives: We set out to investigate the effect of GBP on enteroendocrine cells in the stomach and intestine of pigs. Methods: Lean non-diabetic pigs were subjected to either GBP or sham-surgery and immunocytochemistry and morphometry for all major gut hormones in all parts of the GI-tract was performed. Sham-operated, pair-fed pigs were used as controls. Results: Postoperatively in the antrum, the density of gastrin-cells was lower (GBP 12.8±2.1 cells/μm2 versus sham 21.3±2.6 cells/μm2 ) while density of serotonin-cells was higher in GBP-pigs (GBP 21.6±2.3 cells/μm2 versus sham 10.6±0.7 cells/μm2). In the fundus, no effect of GBP was observed on any cell population. In the duodenum, densities of CCK- (GBP 5.1±1.0 cells/μm2 versus sham 2.6±0.4 cells/μm2), ghrelin- (GBP 3.4±0.5 cells/μm2 versus sham 1.4±0.2 cells/μm2), GIP- (GBP 5.5±0.3 cells/μm2 versus sham 2.3±0.3 cells/μm2) and neurotensin-cells (GBP 3.5±0.7 cells/μm2 versus sham 0.5±0.2 cells/μm2) were higher in the GBP-pigs. In the distal jejunum, density of ghrelin-cells was lower (GBP 0.7±0.2 cells/μm2 versus sham 2.3±0.4 cells/μm2) while densities of GIP- (GBP 3.5±0.3 cells/μm2 versus sham 2.4±0.2 cells/μm2) and secretin-cells (GBP 3.4±0.7 cells/μm2 versus sham 1.6±0.3 cells/ μm2) were higher in GBP-pigs compared to sham-pigs. In the ileum, densities of GIP-cells (GBP 5.4±0.4 cells/ μm2 versus sham 3.9±0.4 cells/μm2) and somatostatin-cells (GBP 3.3±0.4 cells/μm2 versus sham 2.1±0.3 cells/μm2) were higher, while densities of GLP-1-cells (GBP 5.0±0.5 cells/μm2 versus sham 8.8±1.4 cells/μm2) and PYYimmunoreactive cells (GBP 3.8±0.1 cells/μm2 versus sham 5.9±0.8 cells/μm2) were lower in the GBP-pigs. In the colon, densities of GIP- (GBP 2.8±0.3 cells/μm2 versus sham 1.4±0.2 cells/μm2), serotonin- (GBP 6.7±0.3 cells/μm2 versus sham 4.8±0.5 cells/μm2) and somatostatin-cells (GBP 1.9±0.2 cells/μm2 versus sham 1.3±0.1 cells/μm2) were higher in the GBP-pigs. GBP had no effect on villi length or total mucosa height in any of the intestinal segments analyzed, whereas duodenum (GBP 37.6±3.4 cells/μm2 versus sham 26.5±2.8 cells/μm2) and ileum (GBP 127±1.2 cells/μm2 versus sham 84.7±9.9 cells/μm2) of the GBP-pigs displayed higher proliferation, as assessed by Ki67 immunoreactivity. Conclusions: We conclude that GBP induces rapid and profound changes in the densities of gut hormoneproducing cells throughout the GI-tract in pigs. These changes seem to be the result of GBP per se and not a result of body weight or food intake. Also, GIP was increased in the GBP-pigs in all the intestinal segments analyzed.