Jejunoileal bypass changes the duodenal cholecystokinin and somatostatin cell density

Background: In obese patients, jejunoileal bypass (JIB) has been used to induce weight reduction. Changes in the neuroendocrine system may be affected by the JIB-operation, because the proximal small intestinal mucosa has a rich supply of endocrine cells and peptidergic nerves. Materials and Methods: In 37 obese patients operated with JIB 1-30 years ago, small intestinal biopsies were taken at the duodeno-jejunal flexure, proximal to the anastomosis and from 5 unoperated obese persons and 20 normal weight patients. The tissue specimens were processed for immunocyto-chemical demonstration of cells/nerves containing: gastrin, cholecystokinin (CCK), secretin, gastric inhibitory peptide (GIP), motilin, somatostatin, serotonin, glicentine, peptide YY (PYY), neurotensin, vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and galanin. The number of different endocrine cell-types were counted per unit length of mucosa, and the density of the peptidergic nerves was assessed semiquantitatively according to a schematic scale. Results: JIB-patients had an increased density of CCK and somatostatin cells in the duodenal mucosa. The CCK cells displayed a changed reaction pattern, with a greater cell number reacting with an antiserum directed towards a non-amidated mid-sequence of procholecystokinin compared with the other groups. In obese unoperated patients, the density of PYY and secretin cells was decreased compared with the JIB-patients and the density of the GIP cells compared with both other groups. Conclusion: JIB induces an up-regulation of somatostatin and CCK precursor-containing cells in the duodenal mucosa. The time duration after the JIB did not seem to influence the results

The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones.

Bariatric surgery for obesity has proved to be an extremely effective method of promoting long-term weight reduction with additional beneficial metabolic effects, such as improved glucose tolerance and remission of type 2 diabetes. A range of bariatric procedures are in common use, including gastric banding, sleeve gastrectomy and the Roux-en-Y gastric bypass. Although the mechanisms underlying the efficacy of bariatric surgery are unclear, gastrointestinal and pancreatic peptides are thought to play an important role. The aim of this review is to summarise the effects of different bariatric surgery procedures upon gastrointestinal and pancreatic peptides, including ghrelin, gastrin, cholecystokinin (CCK), glucose-dependent insulinotropic hormone (GIP), glucagon-like peptide 1 (GLP-1), peptide YY (PYY), oxyntomodulin, insulin, glucagon and somatostatin.Research in the F. Reimann and F.M. Gribble laboratories is funded by the Wellcome Trust (WT084210Z/07/Z and WT088357Z/09/Z), the MRC (MRC_MC_UU_12012/3) and Full4Health (FP7/2011-2015, grant agreement no. 266408). Claire Meek receives additional salary funding from the Wellcome Trust Translational Medicine and Therapeutics Programme, funded by the Wellcome Trust in association with Glaxo SmithKline.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.peptides.2015.08.01

Hypertrophy dependent doubling of L-cells in Roux-en-Y gastric bypass operated rats

BACKGROUND AND AIMS: Roux-en-Y gastric bypass (RYGB) leads to a rapid remission of type 2 diabetes mellitus (T2DM), but the underlying mode of action remains incompletely understood. L-cell derived gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are thought to play a central role in the anti-diabetic effects of RYGB; therefore, an improved understanding of intestinal endocrine L-cell adaptability is considered pivotal. METHODS: The full rostrocaudal extension of the gut was analyzed in rats after RYGB and in sham-operated controls ad libitum fed or food restricted to match the body weight of RYGB rats. Total number of L-cells, as well as regional numbers, densities and mucosa volumes were quantified using stereological methods. Preproglucagon and PYY mRNA transcripts were quantified by qPCR to reflect the total and relative hormone production capacity of the L-cells. RESULTS: RYGB surgery induced hypertrophy of the gut mucosa in the food exposed regions of the small intestine coupled with a doubling in the total number of L-cells. No changes in L-cell density were observed in any region regardless of surgery or food restriction. The total gene expression capacity of the entire gut revealed a near 200% increase in both PYY and preproglucagon mRNA levels in RYGB rats associated with both increased L-cell number as well as region-specific increased transcription per cell. CONCLUSIONS: Collectively, these findings indicate that RYGB in rats is associated with gut hypertrophy, an increase in L-cell number, but not density, and increased PYY and preproglucagon gene expression. This could explain the enhanced gut hormone dynamics seen after RYGB