oxyntomodulin and Postoperative-Complications

Short bowel syndrome (SBS) refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn's disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable. Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 (GLP-2) is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is a trophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor (GLP-2R) remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.

Topics: Animals; Central Nervous System; Enteric Nervous System; Gastrointestinal Hormones; Glucagon-Like Peptide 2; Glucagon-Like Peptide-2 Receptor; Glucagon-Like Peptides; Humans; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Malabsorption Syndromes; Postoperative Complications; Receptors, Glucagon; Short Bowel Syndrome

Diarrhoea, malabsorption and malnutrition characterise the short bowel syndrome. The underlying gastrointestinal disorders, the types of intestinal resections performed and the subsequent pathophysiological situations are reviewed. Recommended therapeutic measures in the postoperative period as well as in the rehabilitation of patients with short bowel syndrome are discussed in more detail. In the postoperative period, parenteral nutrition is essential followed by an enteral diet to stimulate bowel adaptation, reduce fluid loss and increase nutrient absorption. The final diet should be based on the anatomy of the retained bowel (presence or absence of a colon and ileum). The importance of the colon as a digestive organ in patients with short bowel and the need of a low-oxalate diet are underlined. The possible benefit of new treatment options (glutamine, growth hormone and glucagon-like peptide 2) is discussed. Both typical complications of the short bowel syndrome and management of these complications are presented.

Topics: Combined Modality Therapy; Enteral Nutrition; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Glutamine; Growth Hormone; Humans; Intestinal Absorption; Jejunostomy; Oxalates; Parenteral Nutrition, Total; Postoperative Complications; Prognosis; Randomized Controlled Trials as Topic; Short Bowel Syndrome; Treatment Outcome; Water-Electrolyte Balance

An alteration of the enteroinsular axis (EIA) may be an important etiologic factor in postsurgical changes in gastrointestinal (GI) function. In this review, we present recent works, both from our laboratory and others, on how changes in the EIA function may be involved in postsurgical GI complications, especially late dumping syndrome (LDS). We found no or minimal direct role for vagal signals in the control of gastric inhibitory polypeptide (GIP) and enteroglucagon secretion, which regulate EIA function. In gastrectomized patients, it is suggested that the hypersecretion of glicentin and glucagon-like peptide-1 (GLP-1) induced by a rapid arrival of nutrients to the distal gut suppresses glucagon secretion and may be a cause of LDS. In patients who underwent proctocolectomy, we observed no significant postoperative changes in EIA function, although there are some conflicting reports. It seems unlikely that ordinary pancreaticobiliary diversion would cause a significant change in EIA function after an oral glucose load. Our experimental model of ileojejunal transposition produced marked hypersecretion of incretin secreted from the distal gut, which may alter EIA function. Further elucidation of the regulatory mechanism of EIA may provide a new strategy for the medical and surgical treatment of LDS.

Topics: Digestive System Surgical Procedures; Dumping Syndrome; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Neurotransmitter Agents; Pancreas; Peptide Fragments; Postoperative Complications

Topics: Adult; Arcuate Nucleus of Hypothalamus; Binge-Eating Disorder; Craniopharyngioma; Diabetes Insipidus; Diabetes Mellitus; Diabetic Retinopathy; Disorders of Excessive Somnolence; Drug Therapy, Combination; Female; Glucagon-Like Peptides; Hormone Replacement Therapy; Humans; Hypoglycemic Agents; Hypophysectomy; Hypopituitarism; Immunoglobulin Fc Fragments; Obesity; Pituitary Neoplasms; Postoperative Complications; Recombinant Fusion Proteins; Reoperation

Glucagon-like peptide 1 (GLP-1[7-36 amide]) is an incretin hormone primarily synthesized in the lower gut (ileum, colon/rectum). Nevertheless, there is an early increment in plasma GLP-1 immediately after ingesting glucose or mixed meals, before nutrients have entered GLP-1 rich intestinal regions. The responsible signalling pathway between the upper and lower gut is not clear. It was the aim of this study to see, whether small intestinal resection or colonectomy changes GLP-1[7-36 amide] release after oral glucose. In eight healthy controls, in seven patients with inactive Crohn's disease (no surgery), in nine patients each after primarily jejunal or ileal small intestinal resections, and in six colonectomized patients not different in age (p = 0.10), body-mass-index (p = 0.24), waist-hip-ratio (p = 0.43), and HbA1c (p = 0.22), oral glucose tolerance tests (75 g) were performed in the fasting state. GLP-1[7-36 amide], insulin C-peptide, GIP and glucagon (specific (RIAs) were measured over 240 min.. Repeated measures ANOVA, t-test (significance: p < 0.05). A clear and early (peak: 15-30 min) GLP-1[7-36 amide] response was observed in all subjects, without any significant difference between gut-resected and control groups (p = 0.95). There were no significant differences in oral glucose tolerance (p = 0.21) or in the suppression of pancreatic glucagon (p = 0.36). Colonectomized patients had a higher insulin (p = 0.011) and C-peptide (p = 0.0023) response in comparison to all other groups. GIP responses also were higher in the colonectomized patients (p = 0.0005). Inactive Crohn's disease and resections of the small intestine as well as proctocolectomy did not change overall GLP-1[7-36 amide] responses and especially not the early increment after oral glucose. This may indicate release of GLP-1[7-36 amide] after oral glucose from the small number of GLP-1[7-36 amide] producing L-cells in the upper gut rather than from the main source in the ileum, colon and rectum. Colonectomized patients are characterized by insulin hypersecretion, which in combination with their normal oral glucose tolerance possibly indicates a reduced insulin sensitivity in this patient group. GIP may play a role in mediating insulin hypersecretion in these patients.

Topics: Adult; Aged; C-Peptide; Colectomy; Crohn Disease; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose Tolerance Test; Humans; Insulin; Intestine, Large; Intestine, Small; Male; Middle Aged; Peptide Fragments; Postoperative Complications

In a preliminary study the effect of an aperitif of a stable fat emulsion on symptoms, gastric emptying of a hypertonic glucose meal and associated release of insulin, neurotensin, enteroglucagon, gastric inhibitory polypeptide (GIP) and vasoactive intestinal polypeptide (VIP) was evaluated in 9 patients with postprandial gastrointestinal discomfort after vagotomy. In each patient gastric emptying of the glucose meal was measured twice: 20 min after intake of distilled water and after fat emulsion. On both occasions neurotensin, enteroglucagon and GIP rose significantly from fasting values. In contrast to distilled water, the fat emulsion was able to significantly activate the release of the hormones before ingestion of the glucose meal. All the patients had a rapid emptying of the glucose meal after distilled water and they experienced symptoms that corresponded with the nature of their spontaneous symptoms after ordinary meals. The fat emulsion reduced the early emptying of the meal and relieved the symptoms of the dumping patients, whereas gastric emptying and symptoms were variable in the patients with diarrhoea and other postvagotomy symptoms. The intake of an aperitif of soya bean oil seems to be an effective treatment only in patients with the dumping syndrome.

Topics: Adult; Aged; Blood Glucose; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Insulin; Male; Middle Aged; Neurotensin; Plant Oils; Postoperative Complications; Soybean Oil; Vagotomy; Vasoactive Intestinal Peptide