Release of peptide YY (PYY) after resection of small bowel, colon, or pancreas in man.

To investigate the possible role of peptide YY (PYY) in the adaptive changes that accompany enterectomy, plasma levels of this peptide were measured during breakfast in patients with resected small or large intestines and in controls. In 18 patients who had undergone partial ileal resection, basal PYY concentrations were greatly elevated when compared with controls (51.4 +/- 8.7 pmol/L versus 10.3 +/- 1.0; p less than 0.001) and the postprandial response was similarly increased. In contrast, PYY concentrations were low in 16 patients who had undergone colonic resection and ileostomy (fasting 7.1 +/- 0.7 pmol/L, p less than 0.01). In eight patients who had undergone pancreatectomies, basal and postprandial PYY levels were moderately increased (23.4 +/- 3.5 pmol/L; fasting p less than 0.001). PYY does not appear to have a role in the adaptive trophic response after small intestinal resection, but it may contribute to reduction of gastric secretion and gastrointestinal transit in these patients.

Peptide YY abnormalities in gastrointestinal diseases.

Plasma concentrations of peptide YY (PYY), a newly isolated peptide produced by ileal and colonic endocrine cells, were measured in several groups of patients with digestive disorders after a standardized normal breakfast. Peptide YY levels were found to be grossly elevated in patients with steatorrhea due to small intestinal mucosal atrophy (tropical sprue). Basal levels in these patients were 79 +/- 18 pM, which was nearly 10-fold higher than those seen in healthy controls (8.5 +/- 0.8 pM). Patients with steatorrhea due to chronic destructive pancreatitis also had substantially increased basal PYY levels (47.5 +/- 6.3 pM), and their postprandial response was also greater than that of normal subjects. Moderately elevated plasma PYY concentrations were seen in patients with inflammatory bowel disease and patients recovering from acute infective diarrhea. In contrast, patients with diverticular disease, duodenal ulcer, and functional bowel disease had normal PYY responses. These changes in the secretion of PYY responses. These changes in the secretion, may shed light on the physiologic role of this newly discovered peptide and on intestinal adaptation to common digestive disorders.

Disparity between glucose-dependent insulinotropic polypeptide and insulin responses in obese man.

Studies were carried out in 32 obese patients and 30 normal-weight control subjects to ascertain the response of glucose-dependent insulinotropic polypeptide (GIP) and insulin to (1) oral and intravenous glucose (10 obese and 10 control subjects), (2) oral fat and intravenous glucose (eight obese and six control subjects) and (3) mixed test meal (14 obese and 14 control subjects). Basal mean insulin was higher in the obese (99 pmol/l) than in the control group (40 pmol/l), but fasting blood glucose and GIP were not significantly different from normal. The total integrated response of insulin in obese subjects after oral glucose was 54.1 versus 33.3 nmol . l-1 . h-1 in control subjects; glucose and GIP responses were similar in both groups. After intravenous glucose the integrated insulin response was 8.8 in the obese versus 5.0 nmol . l-1 . h-1 in control subjects; GIP was unaffected by intravenous glucose and glucose levels were similar. Following oral fat and intravenous glucose, insulin secretion was again abnormal in the obese, 24.5 versus 7.3 nmol . l-1 . h-1 in controls, but GIP responses were normal. However, the control subjects became hypoglycaemic after this test: blood glucose 2.8 mmol/l at 150 min compared with 4.6 mmol/l in the obese group. The insulin response to a mixed meal was also abnormal in obesity.

Gut hormones in inflammatory bowel disease.

We have studied fasting levels and the response to a standard test breakfast of blood glucose and several gut hormones in 24 patients with ulcerative colitis, in 14 patients with Crohn's disease, and in 14 healthy control subjects. Patients with ulcerative colitis had significantly elevated fasting human pancreatic polypeptide (HPP) concentrations, and both basal and postprandial levels of gastrin, gastric inhibitory polypeptide (GIP), and motilin were greater than normal. In contrast, patients with Crohn's disease had normal gastrin levels but had increased fasting and postprandial levels of GIP and motilin and, in addition, of enteroglucagon, compared with controls. These patients also had greater than normal HPP concentrations 30 min after the breakfast. Normal levels of insulin, pancreatic glucagon, neurotensin, and vasoactive intestinal polypeptide were found in both groups of patients. Much remains to be known about the pathophysiology of these two debilitating diseases, and the abnormal release of gut hormones may be of importance.

Gut hormones in acute diarrhoea.

The gut hormone response to a breakfast meal was studied in 12 subjects hospitalised for an episode of acute diarrhoea (presumed infective) who were otherwise well and in 13 healthy control subjects. Fasting blood glucose concentrations were low but basal insulin concentrations were raised. Basal concentrations of pancreatic polypeptide and both basal and postprandial responses of motilin, enteroglucagon, and vasoactive intestinal polypeptide (VIP) were also significantly greater than controls. No abnormalities in plasma concentrations of gastrin, gastric inhibitory polypeptide (GIP) or pancreatic glucagon were found. The suggested physiological actions of the raised hormones may be relevant to the pathophysiology of diarrhoea.

Gut hormone release after intestinal resection.

To investigate the possible role of gut and pancreatic hormones in the adaptive responses to gut resection, plasma concentrations of the circulating hormones were measured, in response to a test breakfast, in patients with either small or large intestinal resection and in healthy control subjects. In 18 patients with partial ileal resection a significant threefold rise was found in basal and postprandial levels of pancreatic polypeptide, a fourfold increase in motilin, and more than a twofold increase in gastrin and enteroglucagon levels compared with healthy controls. In contrast, nine patients with colonic resection had a threefold rise in levels of pancreatic polypeptide only. One or more of these peptides may have a role in stimulating the adaptive changes found after gut resection.

Pancreatic and gastrointestinal hormones in chronic pancreatitis.

Pancreatic and gut hormones have been measured in 39 patients with chronic pancreatitis, 16 of whom had severe pancreatic insufficiency. Patients with pancreatic insufficiency had significantly diminished fasting levels and postprandial rises of pancreatic polypeptide which were less than 20% of normal. Patients with chronic pancreatitis, with or without exocrine insufficiency, had two- to threefold higher plasma levels of motilin and enteroglucagon than controls. Plasma levels of insulin, pancreatic glucagon, gastric inhibitory polypeptide and gastrin were similar to normal in these patients. The pattern of response of these hormones to a test breakfast differs markedly from those seen in other gut disease states and may reflect pathophysiological mechanisms.

Colonic inhibition of gastric secretion in man.

The effect of colonic infusion of various solutions on submaximal pentagastrin-stimulated gastric secretion was determined in healthy volunteers. Hypertonic (823 mOsm/kg) glucose, mannitol, and saline, and also isotonic glucose significantly induced a marked and sustained inhibition of gastric acid secretion of 74%, 66%, 79%, and 54%, respectively. A similar degree of inhibition was obtained for pepsin secretion with hypertonic glucose and mannitol. Isotonic triglycerides and isotonic saline solutions had no significant effect on gastric acid secretion. Hypertonic glucose, mannitol, and saline infusions significantly increased plasma concentrations of enteroglucagon, whereas other solutions had no effect. No correlation, however, was found between the percentage rise of enteroglucagon and the percentage inhibition of gastric secretion obtained from any of the three hypertonic solutions. The physiological significance of these findings remains to be established.

Gut-hormone profile in totally pancreatectomised patients.

In eight totally pancreatectomised patients the release of the relevant gut hormones was determined after a standard test meal. Plasma levels of pancreatic glucagon were not significantly different from zero in our series of pancreatectomised patients. Pancreatic polypeptide was undetectable. These findings imply the absence of a significant number of normally functioning alpha cells and pancreatic polypeptide cells in extrapancreatic sites in man. Consistent with the antrectomy, duodenectomy, and resection of the upper jejunum that are performed in conjunction with a total pancreatectomy the gastrin release was significantly impaired. In contrast there was a striking post-prandial rise in enteroglucagon probably induced by the rapid intestinal transit time often seen after partial gastrectomy. In contrast plasma motilin and GIP levels were normal. Pancreatectomised man thus presents an interesting model of total deficiency of endogenous insulin, pancreatic polypeptide, and pancreatic glucagon and, in addition, greatly diminished gastrin. The considerable derangement of metabolic and intestinal function that follows total pancreatectomy may, in part, be explained by this gross disturbance of the normal physiology of gut hormone.

Gut hormone responses in the irritable bowel syndrome.

Fasting and postprandial levels of gastrin, insulin, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, enteroglucagon and neurotensin were measured in 42 patients with irritable bowel syndrome (IBS). No overall major abnormalities of secretion of any of these peptides were found, although minor differences from normal of pancreatic polypeptide and neurotensin were observed. It is doubtful whether abnormalities of gut hormone secretion play an important role in the pathophysiology of IBS.

Gut hormones in tropical malabsorption.

Concentrations of various gut hormones were measured after a test breakfast in eight patients with severe tropical malabsorption and 12 controls. The patients with tropical malabsorption had greatly raised basal plasma motilin and enteroglucagon concentrations, but their postprandial release of both gastric inhibitory polypeptide and insulin was significantly reduced. The pattern of gut hormone release differed from that found in coeliac disease. The measurement of gut hormones, each of which has a specific site and function, thus throws new light on the pathophysiology of tropical malabsorption and may suggest approaches of treatment.

Plasma trypsin in chronic pancreatitis and pancreatic adenocarcinoma.

We have used a simple and precise radioimmunoassay to measure trypsin in human plasma. Fasting plasma trypsin concentrations were extremely low in patients with chronic pancreatitis with steatorrhoea (5 +/- 2 ng/ml) when compared to healthy controls (86 +/- 7 ng/ml, p less than 0.001). In patients with chronic pancreatitis but no steatorrhoea basal plasma trypsin levels were similar to those of the normal controls (99 +/- 25 ng/ml). A small but significant postprandial rise in plasma trypsin concentrations was observed in normal subjects (mean increment 15 +/- 4%, p less than 0.005, paired t test) but was absent in patients with chronic pancreatitis with steatorrhoea. In contrast to exocrine deficient chronic pancreatitis, other malabsorptive conditions associated with steatorrhoea (active coeliac disease and acute tropical sprue) demonstrated mean fasting trypsin concentrations similar to controls. Patients with adenocarcinoma of the pancreas had basal trypsin concentrations similar to healthy subjects as did patients with adenocarcinoma of the stomach, colon, rectum, brochus, and breast. In some cases measurement of plasma trypsin may be of help in the differential diagnosis of steatorrhoea.

Release of motilin by oral and intravenous nutrients in man.

Motilin is a hormonal peptide found in the duodenum and jejunum which potently influences gastrointestinal tract motility. Its role in human physiology is not yet established. After a standard hospital lunch the plasma concentration of motilin showed a small, transient, but significant rise in 28 healthy subjects. Individual food components either stimulated (oral fat) or suppressed release (oral glucose). Plasma motilin levels were, in addition, altered to an equal extent by intravenous nutrients, with glucose and amino acids suppressing release, and intravenous fat causing a significant rise in plasma concentration. These results demonstrate a consistent response to food stimuli, whether oral or intravenous. The release mechanism appears to be complicated and after a balanced meal, containing food components which both stimulate and suppress release, there is only a small net change.

Impaired pancreatic polypeptide release in chronic pancreatitis with steatorrhoea.

Pancreatic polypeptide (PP) is a newly discovered hormonal peptide localised in a distinct endocrine cell type in the pancreas. PP circulates in plasma and in normal subjects levels rise substantially on the ingestion of food (mean rise 138 pmol/l). In 10 patients with chronic pancreatitis with exocrine deficiency the PP response to a test breakfast was greatly reduced (mean rise 20 pmol/l, P less than 0.001). PP response to the meal was normal in 10 patients with active coeliac disease and 12 patients with acute tropical sprue with steatorrhoea.

Inhibition of secretin stimulated pancreatic secretion by pancreatic polypeptide.

The effect of PP on secretin-stimulated pancreatic secretion was assessed in five healthy subjects. During an intravenous infusion of BPP at a dose which produced plasma levels similar to those seen after meals in healthy young adults the volume and bicarbonate content of duodenal juice was reduced by 25% (p less than 0.05) and 24% (p less than 0.05) respectively, while protein and bilirubin concentrations were more markedly reduced by 68% (p less than 0.0005) and 67% (p less than 0.0005) respectively. PP, thus, may be an important inhibitory factor in the control of bilirubin and pancreatic enzyme secretion in man.