peptide-yy and Gastric-Fistula

Weight regain after gastric bypass (GBP) can be associated with a gastrogastric fistula (GGF), in which a channel forms between the gastric pouch and gastric remnant, allowing nutrients to pass through the "old route" rather than bypassing the duodenum. To further understand the mechanisms by which GGF may lead to weight regain, we investigated gut hormone levels in GBP patients with a GGF, before and after repair.. Seven post-GBP subjects diagnosed with GGF were studied before and 4 months after GGF repair. Another cohort of 22 GBP control subjects without GGF complication were studied before and 1 year post-GBP. All subjects underwent a 50-g oral glucose tolerance test and blood was collected from 0-120 min for glucose, insulin, ghrelin, PYY3-36, GIP, and GLP-1 levels.. Four months after GGF repair subjects lost 6.0 ± 3.9 kg and had significantly increased postprandial PYY3-36 levels. After GGF repair, fasting and postprandial ghrelin levels decreased and were strongly correlated with weight loss. The insulin response to glucose also tended to be increased after GGF repair, however no concomitant increase in GLP-1 was observed. Compared to the post-GBP group, GLP-1 and PYY3-36 levels were significantly lower before GGF repair; however, after GGF repair, PYY3-36 levels were no longer lower than the post-GBP group.. These data utilize the GGF model to highlight the possible role of duodenal shunting as a mechanism of sustained weight loss after GBP, and lend support to the potential link between blunted satiety peptide release and weight regain.

Topics: Adult; Blood Glucose; Body Mass Index; Endoscopy, Gastrointestinal; Female; Gastric Bypass; Gastric Fistula; Gastrointestinal Hormones; Gastroscopy; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Laparoscopy; Male; Obesity, Morbid; Peptide Fragments; Peptide YY; Postoperative Complications; Postoperative Period; Preoperative Period; Suture Techniques; Time Factors; Treatment Outcome; United States; Weight Loss

Peptide YY (PYY) is released from the gut after ingestion of fat or after a meal. The purpose of this investigation was to examine the effect of PYY on gastric inhibitory polypeptide (GIP)-stimulated insulin release in conscious dogs with gastric and duodenal fistulas. In control experiments, 6 dogs received GIP (400 pmol/kg, i.v., for 1 h) and glucose (0.6 g/kg, i.v., for 1 h); the integrated insulin response over a 1-h period was 142 +/- 32.7 ng-60 min/ml. The plasma GIP levels achieved by this procedure were similar to those observed by intraduodenal infusion of Lipomul (2 ml/min), suggesting that the dose of GIP used was within the physiologic range. Intravenous infusion of three different doses of PYY (100, 200, or 400 pmol/kg.h) caused a significant inhibition of insulin release stimulated by GIP + glucose; the integrated insulin response was reduced to 105, 88, and 79 ng-60 min/ml, respectively. On the other hand, PYY (400 pmol/kg.h) had no effect on insulin secretion induced by intravenous glucose (0.6 g/kg.h) alone. These results indicate that PYY specifically inhibits the insulinotropic action of GIP and that PYY may play a negative-feedback regulatory role in the enteroinsular axis.

Topics: Animals; Blood Glucose; Dogs; Duodenal Diseases; Female; Gastric Fistula; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Insulin; Intestinal Fistula; Male; Peptide YY; Peptides; Stimulation, Chemical