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Six duodenal ulcer patients were investigated before and 3 months after truncal vagotomy and pyloroplasty. Plasma concentrations of gastric inhibitory polypeptide (GIP), insulin, and glucose were measured during intrajejunal infusion of 50 g of glucose. The GIP response was significantly diminished postoperatively; insulin and glucose concentrations, however, were unchanged. The reduction of GIP release was positively correlated with the reduction of the peak acid output. The results suggest that a reduced vagal innervation of the intestine is accompanied by reduced GIP release after intrajejunal glucose, depending on the degree of completeness of vagotomy.

The responses of gastric inhibitory polypeptide (GIP) and insulin to intraduodenal and IV triglyceride infusions were measured in 11 late fetal and 10 neonatal pigs. Basal plasma glucose, insulin, and GIP concentrations were lower in fetal than in neonatal pigs. In the fetal pigs, plasma glucose increased slightly during intraduodenal and IV triglyceride infusions, whereas plasma insulin remained unchanged during the tests. No significant changes were observed in plasma GIP concentration following intraduodenal triglyceride infusion in the fetal pigs, but plasma GIP fell during the IV infusion of triglyceride in these pigs (p less than 0.01). In the neonatal pigs, plasma glucose and insulin remained unaffected by intraduodenal and triglyceride infusions. Plasma GIP did not change during the IV triglyceride infusion, but exhibited a paradoxical decline after the intraduodenal triglyceride infusion (p less than 0.05). It is concluded that the GIP-cell response to an oral triglyceride load is suppressed in late fetal and neonatal pigs. The abolished GIP response to oral triglycerides could play a causal role in the inactivity of the enteroinsular axis which is seen in both human and animal neonates.

The effect of gastric inhibitory polypeptide (GIP) in physiological concentrations (250, 500, 1,000 and 2,000 pg/ml) upon endocrine and exocrine secretion from the isolated perfused porcine pancreas was studied at various glucose concentrations in the perfusate. GIP increased insulin release in a dose-dependent manner. The sensitivity of the beta-cells to GIP was glucose independent. No effect was observed on glucagon or exocrine secretion regardless of the glucose concentration in the perfusate. We conclude that GIP is powerful insulin-stimulator even in low physiological concentrations in the presence of glucose concentrations comparable to those seen during an oral glucose load, which makes GIP to one of the strongest incretin candidates known, i.e. the factor(s) contributing to the augmented insulin response after ingestion of glucose.

The effect of gastrin-releasing peptide (GRP) on pancreatic exocrine secretion was studied by infusing it at four dose levels (0.01, 0.1, 1.0, and 10 nmol/l) into the arterial line of the isolated perfused porcine pancreas. At 1.0 nmol/l GRP stimulated protein (37-fold), fluid (13-fold), and bicarbonate secretion (12-fold). Atropine at 1 mumol/l diminished the protein secretion in response to infusion of GRP at a dose of 1 nmol/l to 45% of control. Fluid and bicarbonate responses were not affected by atropine treatment. Electrical stimulation of the vagus nerves resulted in an increase in pancreatic output of GRP and a concomitant stimulation of exocrine secretion. Infusions of acetylcholine, carbachol, pilocarpine, or dimethylphenylpiperazinium had no effect on the output of GRP, although hexamethonium abolished the response to vagal stimulation. It is concluded that GRP in conjunction with acetylcholine is likely to play a prominent part in parasympathetic regulation of pancreatic exocrine secretion.

The role of nerves that liberate vasoactive intestinal polypeptide (VIP) in the porcine pancrease as mediators of the atropine-resistant action of the vagus on flow and bicarbonate (HCO3) secretion was examined. Efferent electrical stimulation of the vagus in atropinized pigs produced a profuse flow of pancreatic juice with high HCO3 content concomitantly with a significant increase in pancreatic VIP output from 13 to 113 fmol/min. Intravenous administration of somatostatin (SRIF) during continuous electrical vagal stimulation caused a parallel suppression of the VIP release and the pancreatic fluid and HCO3 secretion to prestimulatory values. The SRIF-induced reduction in fluid and HCO3 secretion seemed to be mediated via an inhibition of the VIP release rather than through a direct effect on the exocrine cells, inasmuch as SRIF did not influence the VIP-provoked exocrine response from the in vitro isolated perfused porcine pancreas. The results support the view that VIP is transmitter in the vagally induced atropine-resistant water and HCO3 secretion from the porcine pancreas.

The responses of gastric inhibitory polypeptide (GIP) and insulin to intraduodenal (OGTT) and iv (IVGI) glucose infusions were measured in 14 late fetal and 9 neonatal pigs. Basal plasma glucose (P < 0.01) and GIP (P < 0.001) concentrations were lower in the fetal than in the neonatal pigs, while basal plasma insulin was not significantly different in the two groups. In the fetal pigs, almost identical plasma glucose curves were obtained during the OGTT and the IVGI, but plasma insulin did not change during either test. In these pigs, plasma GIP increased 3-fold (P < 0.01) during the OGTT, whereas no significant changes in plasma GIP were observed during the IVGI. In the neonatal pigs, plasma glucose increased more during the OGTT than during the IVGI, but plasma insulin exhibited similar increments during both tests. Thus, the insulinogenic index of the IVGI was almost 3 times higher than that of the OGTT (P < 0.05). In contrast to the normal increment in plasma GIP observed in fetal pigs, plasma GIP decreased significantly during both tests in the neonatal pigs. It is concluded that beta-cells of fetal pigs are unresponsive to acute elevations of plasma glucose with or without a concomitant increase in plasma GIP. Conversely, beta-cells of neonatal pigs exhibit a significant response to hyperglycemia, but the enteroinsular axis is defective, since more insulin is released after iv than during intraduodenal glucose administration. The defective enteroinsular axis in neonatal pigs might be due to the observed fall in plasma GIP during the OGTT.

The secretion of gastric inhibitory polypeptide and of insulin was studied in patients with chronic relapsing pancreatitis and a healthy controls in the fasting state as well as after the oral intake of glucose. The basal levels of gastric inhibitory polypeptide were significantly lowered in patients with chronic relapsing pancreatitis compared with levels in normal persons, whereas the basal insulin levels were normal. The gastric inhibitory polypeptide response to orally administered glucose in patients with pancreatitis exhibited a paradoxic decline and was significantly lower than it was in normal persons. Patients with pancreatitis also had a diminished insulin response to glucose. The findings suggest that the feedback mechanisms between gastric inhibitory polypeptide and insulin, seen in normal persons, are not functioning in patients with chronic relapsing pancreatitis. The events which cause this are, at present, unknown.

We previously showed that basal and pentagastrin-stimulated gastric acid secretion, gastrin in serum and gastrin in antral mucosa were significantly greater in patients with Roux-Y hepaticojejunostomy than in those with choledochoduodenostomy. These findings prompted investigation of basal secretion of gastric inhibitory polypeptide (a peptide with an enterogastrone as well as an insulinogenic effect), insulin and glucose in the same patients. Basal gastric inhibitory polypeptide was significantly lower in patients with Roux-Y hepaticojejunostomy than in those with choledochoduodensotomy, whereas glucose and insulin did not differ in the two groups. No correlation could be demonstrated between gastric inhibitory polypeptide, gastric acid secretion and gastrin, suggesting that hyposecretion of gastric inhibitory polypeptide is not a pathogenetic factor for the hypersecretion of gastric acid secretion in patients with Roux-Y hepaticojejunostomy. Hyposecretion of gastric inhibitory polypeptide and gastric acid hypersecretion in patients with bile diversion seem to be two independent phenomena.

We studied the secretion of insulin, glucagon, and the exocrine secretion of the isolated perfused porcine pancreas in response to vasoactive intestinal polypeptide (VIP) in concentrations ranging from 30 to 18,750 pmol/liter at various concentrations of glucose in the perfusion medium. VIP stimulated the insulin and glucagon secretion in a dose-dependent manner. The response pattern was critically dependent on the glucose concentration. In the presence of a glucose concentration of 7.5 mmol/liter, VIP enhanced insulin release without affecting glucagon release. Maximal insulin release was obtained at a VIP concentration of 3,750 pmol/liter. At a glucose concentration of 5.0 or 3.5 mmol/liter, VIP enhanced glucagon release but not insulin release. VIP stimulated the exocrine secretion in a secretin-like manner. The lowest concentration of VIP observed to increase pancreatic exocrine secretion was 30 pmol/liter, whereas the maximal pancreatic exocrine responses were not obtained.

The porcine antrum was isolated with the pancreas and perfused in vitro with an artificial medium supplemented with erythrocytes. The vagal innervation was preserved. Effluent was collected from the portal vein as well as from a vein directly draining the antrum. Electrical vagal stimulation increased gastrin output and inhibited somatostatin output. Intraluminal hydrochloric acid had the opposite effect. Gastric inhibitory polypeptide (GIP) in physiological concentrations (90 and 450 pmol/l) increased somatostatin output, inhibited gastrin output, and potentiated the effect of HCl on somatostatin release. Vagal stimulation, however, abolished the GIP effect on somatostatin output. Thus gastrin and somatostatin outputs were always inversely affected by the applied stimuli, suggestive of somatostatin-mediated control of gastrin secretion. GIP may exert its effects via local somatostatin release.