The Roux-en-Y Gastric Bypass (RYGB) operation for obesity results in sustained weight loss and improvements in carbohydrate tolerance, that no current medical treatment can replicate. The mechanism that underlies the metabolic improvements observed after RYGB remains unclear, but there is an association with increased post-prandial concentrations of several gut hormones; glucagon like peptide-1 (GLP-1), oxyntomodulin (OXM), peptide YY (PYY) and glucagon. Each of these hormones have multiple and different actions that include reductions in food intake, increases in energy expenditure, satiety and improvements in glucose tolerance. Previous studies investigating the metabolic effects of these hormones have used single or dual infusions.
In this thesis, I have investigated for the first time the effect of co-infusing three gut hormones; GLP-1, OXM and PYY together on food intake. The dose used of each hormone was designed to replicate the postprandial levels observed after RYGB. This triple hormone infusion resulted in a significant reduction in food intake relative to saline and subsequently supports the role of gut hormones in the metabolic benefits observed after RYGB
In addition, I have also investigated the effect of co-infusing GLP-1 and glucagon on carbohydrate tolerance. Glucagon is elevated post RYGB but is known to increase plasma glucose by promoting glycogenolysis and gluconeogenesis This conflicts with the improved glucose tolerance observed post RYGB. I have demonstrated for the first time that co-infusion of GLP-1 and glucagon results in improved glucose tolerance.
Finally, I have investigated a metabolic complication of RYGB in which gut hormones have been implicated, postprandial hypoglycaemia (PPH). In this thesis, I have shown an association between PPH and elevated GLP-1 and glucagon. These data provide a potential target for treating PPH as well as demonstrating a potential adverse event of elevated gut hormone concentrations.Open Acces
