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Blockade of actions from only one of the two L-cell hormones, GLP-1 and PYY, resulted in concomitant increased secretion of the other, probably explaining the absent effect on food intake on these experimental days. Combined blockade of GLP-1 and PYY actions increased food intake after RYGB, supporting that these hormones have a role in decreased food intake postoperatively.

Gastric bypass surgery leads to profound changes in the secretion of gut hormones with effects on metabolism, appetite, and food intake. Here, we discuss their contributions to the improvement in glucose tolerance and the weight loss that results from the operations. We find that the improved glucose tolerance is due the following events: a negative energy balance and resulting weight loss, which improve first hepatic and later peripheral insulin sensitivity, in combination with increased postprandial insulin secretion elicited particularly by exaggerated glucagon-like peptide-1 responses. The weight loss is due to loss of appetite resulting in reduced energy intake, and we find it probable that this process is driven by exaggerated secretion of appetite-regulating gut hormones including, but probably not limited to, glucagon-like peptide-1 and peptide-YY. The increased secretion is due to an accelerated exposure to and absorption of nutrients in the small intestine. This places the weight loss and the gut hormones in key positions with respect to the metabolic improvements after bypass surgery.

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Bone homeostasis displays a circadian rhythm with increased resorption during the night time as compared to day time, a difference that seems—at least partly—to be caused by food intake during the day. Thus, ingestion of a meal results in a decrease in bone resorption, but people suffering from short bowel syndrome lack this response. Gut hormones, released in response to a meal, contribute to this link between the gut and bone metabolism. The responsible hormones appear to include glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), known as incretin hormones due to their role in regulating glucose homeostasis by enhancing insulin release in response to food intake. They interact with their cognate receptors (GIPR and GLP-1R), which are both members of the class B G protein-coupled receptors (GPCRs), and already recognized as targets for treatment of metabolic diseases, such as type 2 diabetes mellitus (T2DM) and obesity. Glucagon-like peptide-2 (GLP-2), secreted concomitantly with GLP-1, acting via another class B receptor (GLP-2R), is also part of this gut-bone axis. Several studies, including human studies, have indicated that these three hormones inhibit bone resorption and, moreover, that GIP increases bone formation. Another hormone, peptide YY (PYY), is also secreted from the enteroendocrine L-cells (together with GLP-1 and GLP-2), and acts mainly via interaction with the class A GPCR NPY-R2. PYY is best known for its effect on appetite regulation, but recent studies have also shown an effect of PYY on bone metabolism. The aim of this review is to summarize the current knowledge of the actions of GIP, GLP-1, GLP-2, and PYY on bone metabolism, and to discuss future therapies targeting these receptors for the treatment of osteoporosis.

-Exaggerated secretion of glucagon-like peptide 1 (GLP-1) is important for postprandial glucose tolerance after Roux-en-Y gastric bypass (RYGB), whereas the role of glucose-dependent insulinotropic polypeptide (GIP) remains to be resolved. We aimed to explore the relative importance of endogenously secreted GLP-1 and GIP on glucose tolerance and ␤-cell function after RYGB. We used DPP-4 inhibition to enhance concentrations of intact GIP and GLP-1 and the GLP-1 receptor antagonist exendin-(9 -39) (Ex-9) for specific blockage of GLP-1 actions. Twelve glucose-tolerant patients were studied after RYGB in a randomized, placebo-controlled, 4-day crossover study with standard mixed-meal tests and concurrent administration of placebo, oral sitagliptin, Ex-9 infusion, or combined Ex-9-sitagliptin. GLP-1 receptor antagonism increased glucose excursions, clearly attenuated ␤-cell function, and aggravated postprandial hyperglucagonemia compared with placebo, whereas sitagliptin had no effect despite two-to threefold increased concentrations of intact GLP-1 and GIP. Similarly, sitagliptin did not affect glucose tolerance or ␤-cell function during GLP-1R blockage. This study confirms the importance of GLP-1 for glucose tolerance after RYGB via increased insulin and attenuated glucagon secretion in the postprandial state, whereas amplification of the GIP signal (or other DPP-4-sensitive glucose-lowering mechanisms) did not appear to contribute to the improved glucose tolerance seen after RYGB.Roux-en-Y gastric bypass; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; exendin-(9 -39); dipeptidyl peptidase-4 inhibition ROUX-EN-Y GASTRIC BYPASS (RYGB) is an effective treatment of severe obesity and induces large and sustainable weight loss, which is superior to diet, intensive lifestyle, or pharmaceutical interventions (47, 51). Moreover, RYGB improves glycemic control within days after surgery, before major weight loss (24), and induces remission of type 2 diabetes in the majority of patients (5, 47). Patients with preoperative normal glucose tolerance (NGT) also display changed postprandial glycemic profile after RYGB with increased peak plasma glucose, followed by a lower nadir (24,45). A combination of improved hepatic insulin sensitivity induced by hypocaloric postoperative diet (18), rapid glucose absorption (19), and exaggerated postprandial insulin secretion seems to be responsible for the early changes in glucose metabolism after RYGB in patients with NGT and type 2 diabetes (3).The postprandial gastrointestinally induced stimulation of insulin secretion, the incretin effect, is due to the insulinotropic effects of the two hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) (38,56). In glucose-tolerant subjects, GLP-1 and GIP contribute nearly equally to the incretin effect, which explains up to 70% of the postprandial insulin secretion (36,38,56). The incretin effect is severely impaired in type 2 diabetes (35) but is also reduced in obese people with NGT ...

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Laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (SG) are the three most commonly performed bariatric procedures. Obesity responds well to bariatric surgery, with major long-lasting weight loss that is most pronounced after RYGB and SG, where the mean weight loss is about 40 kg or 15 body mass index (BMI) units. Some of the benefits after RYGB and SG are independent of weight loss, and the remission of type 2 diabetes is observed a few days after the operation; this depends on changes in insulin sensitivity and gut hormone responses, especially a 10-fold increase in glucagon-like peptide-1 (GLP-1), which improves insulin secretion. After gastric banding, the remission of diabetes depends more on weight loss. Bariatric surgery reduces cardiovascular risk factors including hypertension, lipid disturbances, non-alcoholic fatty liver, musculoskeletal pain and reduces mortality of diabetes, cardiovascular diseases and cancers. Bariatric surgery also improves quality of life. The acute complications of surgery are infection, bleeding and anastomotic leak. Long-term complications are nutritional deficiencies, including vitamins and minerals, and anemia. Some patients have dumping after meals, and a few patients will develop postprandial hypoglycemia after RYGB. About 25% of patients require plastic surgery to provide relief from excessive skin tissue.