oxyntomodulin and Dumping-Syndrome

Topics: Biomarkers; Diabetes Mellitus; Diagnostic Techniques, Endocrine; Dumping Syndrome; Glucagon; Glucagon-Like Peptides; Glucagonoma; Humans; Liver Diseases; Pancreatic Diseases; Pancreatic Neoplasms; Radioimmunoassay; Reference Values; Specimen Handling

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: Antigens; Chemical Phenomena; Chemistry; Diabetes Mellitus; Dumping Syndrome; Gastrectomy; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Intestine, Small; Obesity; Pancreatitis; Peptides; Radioimmunoassay; Vagotomy

Topics: Blood Glucose; Carbohydrate Metabolism; Dumping Syndrome; Glucagon-Like Peptides; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulin Secretion; Intestinal Absorption

Postprandial glucagon-like peptide-1 (GLP-1), pancreatic glucagon, and insulin were measured in 27 tumor-free patients 43 months (median) after total gastrectomy and in four controls using a 99technetium-labeled 100-g carbohydrate solid test meal. Emptying of the gastric substitute was measured by scintigraphy. Fourteen patients suffered from early dumping symptoms, and five of them also reported symptoms suggestive of reactive hypoglycemia (late dumping). The median emptying half-time (T1/2) of the gastric substitute was 480 sec. Sigstad's dumping score was 8.5 +/- 1.6 (mean +/- SE) in patients with rapid emptying (T1/2 less than 480 sec), and 3.0 +/- 1.5 in patients with slow emptying of the gastric substitute (P = 0.02). The peak postprandial concentration of GLP-1 was 44 +/- 20 pmol/liter in controls, 172 +/- 50 in patients without reactive hypoglycemia, and 502 +/- 116 in patients whose glucose fell below 3.8 mmol/liter during the second postprandial hour. Plasma GLP-1 concentrations peaked at 15 min, and insulin concentrations at 30 min after the end of the meal. A close correlation between integrated GLP-1 responses and integrated insulin responses (r = 0.68) was observed. Multiple regression revealed that three factors were significantly associated with the integrated glucose concentrations during the second hour (60-120 min): Early (first 30 min) integrated GLP-1 (inverse correlation; P = 0.006), age (P = 0.006), and early integrated pancreatic glucagon (P = 0.005). There was a close (inverse) relationship of T1/2 with early integrated GLP-1 and pancreatic glucagon, but not with insulin. Gel filtration of pooled postprandial plasma of gastrectomized individuals revealed that all glucagon-like immunoreactivity eluted at Kd 0.30 (Kd, coefficient of distribution), the elution position of glicentin. Almost all of the GLP-1 like immunoreactivity eluted at Kd 0.60, the elution position of gut GLP-1. The authors contend that GLP-1-induced insulin release and inhibition of pancreatic glucagon both contribute to the reactive hypoglycemia encountered in some patients following gastric surgery. Rapid emptying seems to be one causative factor for the exaggerated GLP-1 release in these subjects.

Topics: Blood Glucose; Dumping Syndrome; Eating; Gastrectomy; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Hypoglycemia; Insulin; Peptide Fragments; Protein Precursors

Topics: Celiac Disease; Dumping Syndrome; Gastrointestinal Hormones; Glucagon-Like Peptides; Glucose; Humans; Radioimmunoassay

A reaction indistinguishable from the early dumping syndrome was induced in four of nine normal volunteers by intraduodenal instillation of a hypertonic glucose meal. Tachycardia and marked peripheral vasodilatation were demonstrated in 'dumpers' by Doppler ultrasound measurements of the arterial blood flow signal. The dumping reaction was not detectably altered by the addition of guar to the meal. Plasma VIP concentration rose and plasma volume fell to a similar degree in 'dumpers' and 'non-dumpers', suggesting that neither event is an integral component of the dumping mechanism. In contrast, the rates of rise of blood glucose and enteroglucagon concentration were markedly greater in 'dumpers'. The results are inconsistent with the conventional explanation that the early dumping syndrome is caused by a large osmotic fluid shift, but are compatible with a mechanism involving an initial period of intestinal hypermotility.

Topics: Blood Flow Velocity; Blood Glucose; Dumping Syndrome; Duodenum; Glucagon-Like Peptides; Glucose Solution, Hypertonic; Heart Rate; Humans; Insulin; Male; Plasma Volume

This study was planned in pursuit of the relation between glucagon responses to glucose and the late dumping syndrome. Clinically, 75 g oral glucose tolerance test to seven late dumpers, ten gastrectomized patients and ten normal subjects were performed. And experimentary, 20 ml 25% glucose was put into small intestinal blind loops prepared in dogs, which were made the jejunum region and then the ileum region. 1. The mean oral glucose tolerance curve in gastrectomized patients was oxyhyperglycemic, and this tendency was seen in late dumpers. But, for only late dumpers, the low blood glucose concentration which was under 50 mg/dl appeared within one and half to three hours after oral glucose load. 2. The change of serum IRI in gastrectomized patients displayed the initial hyperinsulinemia, that was similar in late dumpers. 3. Pancreatic glucagon (GI) levels were within normal limits in normal subjects and late dumpers, but were significantly increased in gastrectomized patients. 4. Enteroglucagon (gutGLI) levels were not so increased in normal subjects, but were significantly increased in gastrectomized patients and late dumpers as well. 5. GutGLI levels were increased only by putting into the ileum loop. But hypersecretion of gutGLI did not affect the blood glucose curve and the change of serum IRI significantly. These results described above suggest that the pathogenesis of the hypoglycemia in the late dumping syndrome may be responsible for no hypersecretion of GI, for some reason, to prevent hypoglycemia against hyperinsulinemia with oxyhyperglycemia, and that gutGLI may not play so important part in the regulation of the blood glucose level.

Topics: Aged; Animals; Blood Glucose; Dogs; Dumping Syndrome; Female; Gastrectomy; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulin Secretion; Male; Middle Aged

Infusion of somatostatin reduced the symptoms of the early dumping syndrome after oral glucose was given and also reduced the associated tachycardia and rise in packed cell volume. It inhibited the secretion of enteroglucagon, neurotensin, and vasoactive intestinal polypeptide, which are raised in patients with the dumping syndrome and may have an aetiological role. It also prevented the reactive hypoglycaemia of late dumping by inhibiting the release of gastric inhibitory polypeptide and insulin. Somatostatin, possibly through its inhibitory effects on hormonal secretion, may have a role in the management of patients with the early and late dumping syndrome.

Topics: Blood Glucose; Dumping Syndrome; Glucagon-Like Peptides; Hematocrit; Humans; Male; Middle Aged; Neurotensin; Somatostatin; Time Factors; Vasoactive Intestinal Peptide

The effect of pectin on gastric emptying, gut hormone release, and symptoms was studied in four patients with dumping syndrome and in two healthy volunteers after ingestion of a hypertonic glucose meal with and without addition of pectin. The initial fraction emptied from the stomach was reduced in the patients, whose symptoms of dumping were abolished or alleviated by pectin. This change of the emptying seems to be caused by a prolonged stomach transit, probably due to the viscous nature of the pectin meal. Pectin had no effect on the gastric emptying of the volunteers. The motor activity of the stomach was not altered by pectin in either the patients or volunteers. In the patients insulin, enteroglucagon, neurotensin, and gastric inhibitory polypeptide rose to higher levels after the glucose meal than after the glucose-pectin meal. The individual differences in the hormone release were considered secondary to the altered gastric emptying produced by pectin.

Topics: Adult; Blood Glucose; Dumping Syndrome; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptides; Glucose Solution, Hypertonic; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Motilin; Neurotensin; Pectins

Insulin, enteroglucagon, neurotensin, gastric inhibitory polypeptide (GIP), and motilin have been measured in plasma during an oral glucose test in 76 patients before or after different upper gastrointestinal operations for peptic ulceration. The patients were divided into three clinical groups in accordance with their spontaneous symptoms of dumping after ordinary meals: 26 postoperative patients into a dumping group, 30 postoperative patients into a non-dumping group, and 20 preoperative patients into a reference group. The fasting values of the five hormones were similar in the operated and non-operated groups. Insulin, enteroglucagon, neurotensin, and GIP rose significantly in all patients. The increment of insulin, enteroglucagon, and neurotensin was greater in the postoperative patients with dumping symptoms than in the postoperative and preoperative patients without dumping symptoms. All the patients had a small decrement of motilin. The resulting hypothesis is that an impaired neural control of the gastric emptying is the essential aetiological factor in the dumping syndrome. The excessively rapid delivery of the meal into the jejunum is the abnormal stimulus to the exaggerated hormone release. The response of the small intestine with regard to the hormone release is considered proportionate to the given stimulus. The abrupt fall in circulating blood volume is suggested to play a role in producing the polymorphic symptoms. Neurotensin and GIP cannot be excluded from being the factors arresting the rapid gastric emptying in patients whose neural control has been impaired after gastric surgery.

Topics: Adult; Aged; Dumping Syndrome; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptides; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Motilin; Neurotensin; Peptic Ulcer; Vagotomy

A means of estimating human enteroglucagon (glucagon-like immunoreactivity of intestinal origin) in tissues and plasma is described, based on the subtraction of RIA values obtained with the C-terminal-directed glucagon antiserum RCS5 from the total glucagon-like immunoreactivity determined with the N-terminal- to midmolecule-directed glucagon antiserum R59. Gel filtration on Sephadex G-50 of human plasma and extracts of normal human intestine separated the R59 immunoreactivity into three peaks: a small peak of void volume material, a major peak coeluting with porcine glicentin, and a smaller peak coeluting with pancreatic glucagon. No RCS5 immunoreactivity was detected in the human gut, except for a small amount constituting less than 2% of the total glucagon-like immunoreactivity in the ileum and rectum only. In extracts of human pancreas, the chromatographic profiles obtained with RCS5 and R59 assays differed from the intestinal patterns, but were identical to each other, giving no evidence of a significant amount of pancreatic R59 immunoreactivity that was not also reactive with RCS5. Chromatography of plasmas from healthy subjects and patients with dumping syndrome, active coeliac disease, and tropical sprue showed that only the second major peak of R59 immunoreactivity reflected the basal or postnutrient increases in the plasma enteroglucagon concentration. In patients with exaggerated enteroglucagon release, the rise was again found to be entirely due to an increase in this peak of immunoreactivity. This major molecular form of human enteroglucagon, similar in size to porcine glicentin, is, thus, the form most likely to be of physiological and pathophysiological significance.

Topics: Adult; Celiac Disease; Chromatography, Gel; Digestive System; Dumping Syndrome; Female; Food; Gastrointestinal Diseases; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Immune Sera; Male; Middle Aged; Pancreas; Radioimmunoassay; Sprue, Tropical; Tissue Distribution

1. The pathophysiology of the dumping syndrome is poorly understood. Plasma levels of four small intestinal hormones have been measured after an oral glucose provocation test in 19 patients with dumping symptoms and in matched controls. 2. Plasma levels of neurotensin, a newly discovered highly potent, hypotensive ileal peptide, were significantly increased in symptomatic patients compared with those of controls [20 min rise of 43 +/- 6.0 (mean +/- SEM) pmol/l in 19 symptomatic patients, 8.0 +/- 5.5 pmol/l in 20 postoperative symptom-free patients, and 4.1 +/- 3.5 pmol/l in 20 pre-operative patients with duodenal ulcer, P < 0.01]. 3. The rise in enteroglucagon was greater than normal but of similar magnitude to that seen in several other gastrointestinal conditions not associated with dumping symptoms. 4. The release of both gastric inhibitory peptide and motilin did not differ significantly from that of controls.

Topics: Blood Glucose; Dumping Syndrome; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptides; Humans; Male; Middle Aged; Motilin; Neurotensin

Topics: Animals; APUD Cells; Chromatography, Gel; Dumping Syndrome; Fluorescent Antibody Technique; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Microscopy, Electron; Radioimmunoassay