Pancreatic polypeptide and gastrin release during sham feeding in man

During modified sham feeding (MSF) the role of endogenous gastric acid secretion and the influences of the autonomic nervous system on the release of pancreatic polypeptide (PP) and gastrin have been studied in 12 healthy subjects (aged 24-38 years). Sham feeding was performed without pretreatment (control) and after pretreatment with 400 mg cimetidine, 80 mg propranolol (both given orally) or 1 mg atropine administered subcutaneously 60 min prior to sham feeding. MSF induced a significant increase (about 100%) in PP release. Its early peak was reduced by pretreatment with propranolol whereas cimetidine had no effect. Atropine completely abolished the PP response. Gastrin release was stimulated by MSF only after prior administration of cimetidine and, to a lesser extent, after atropine pretreatment. It is concluded that: (1) the PP release after stimulation is under strong cholinergic control but is also mediated--particularly in the early phase--by adrenergic mechanisms; (2) endogenously released acid during vagal stimulation plays a minor role in the modulation of PP secretion, but (3) masks gastrin response to MSF.     

Pancreatic secretory response to sham feeding in humans

We studied the pancreatic secretory response to sham feeding alone or during secretin infusion with and without administration of atropine in 10 human subjects. The magnitude of the response to sham feeding was compared to the response to cholecystokinin octapeptide. Sham feeding alone did not significantly increase pancreatic bicarbonate or amylase secretion above basal values. During a background secretin infusion, there was a significant increase of bicarbonate and amylase output (p less than 0.05) during sham feeding. The amylase response was approximately 50% of the maximal response to cholecystokinin octapeptide. In the tests with atropine and secretin, sham feeding still caused a significant increment in amylase and bicarbonate output. We conclude that (1) the pancreatic response to sham feeding is not clearly demonstrated without a background of secretin; (2) during secretin infusion sham feeding is a potent stimulant of pancreatic enzyme secretion, and (3) atropine had no significant effect on the pancreatic response to sham feeding under the conditions of this study.     

Attenuation of gastric sham feeding response during reflex sympathetic activation in man

In six human volunteers we studied the effects of hypovolemia on the secretory activity of the gastric mucosa. The secretion of acid and HCO3 from the stomach was calculated from continuous measurements of pH and Pco2 in gastric effluent. Gastric secretion was stimulated by sham feeding (SF), and cardiac filling pressure was decreased by pooling blood in the lower extremities (lower body negative pressure (LBNP]. LBNP at -20 mmHg had no significant effects on systemic arterial pressure or heart rate but increased plasma norepinephrine concentration by 48 +/- 6% (p less than 0.001). Both the acid and the alkaline responses to SF were significantly attenuated during LBNP (-38 +/- 8%, p less than 0.01, and -55 +/- 14%, p less than 0.05, respectively). Analysis of the relationship between acid and HCO3 secretion in individual experiments suggested a relatively more pronounced inhibition of HCO3 secretion. The results imply that a decreased responsiveness of the gastric mucosa may be one component of the cardiovascular reflex adaptation to hypovolemia. A downregulation of active secretion will lead to smaller metabolic demands from the secreting cells and may thereby help to maintain a vasoconstriction in the gastric mucosa.     

Gallbladder emptying response to sham feeding in humans

Cholescintigraphy, using 99mTc-HIDA, was employed to determine the gallbladder emptying response to sham feeding of a steak and potato meal, and to compare it with the emptying responses to direct cholinergic stimulation by bethanechol and to ingestion of the test meal. The maximal cumulative gallbladder emptying response to sham feeding was 44.1% + 10.1%, which was not significantly different from the response to bethanechol. Cholinergic blockade with atropine eliminated the emptying response to sham feeding. Also, sham feeding did not stimulate gallbladder emptying in patients with vagotomy. This study suggests that intact vagus nerves and cholinergic pathways are required in order for the gallbladder to respond to sham feeding. The precise mechanism for this effect has not been elucidated.     

Mechanism of release of gastric luminal somatostatin-like immunoreactivity in response to pentagastrin and sham feeding in man

We studied in five healthy volunteers whether the cholinergic pathway regulated the secretion of gastric intraluminal somatostatin-like immunoreactivity (SLI) in response to stimuli of pentagastrin infusion (0.9 micrograms/kg/h, intravenously) and sham feeding. We measured gastric secretory volume, hydrogen ion output, and SLI at base line, during pentagastrin infusion, after sham feeding, and after applications of atropine (0.0, 0.7, 7.0 micrograms/kg, intramuscularly) given before pentagastrin and sham feeding. The stimuli were given randomly, at separate times on different days. After each stimulus, eight 15-min gastric juice collections were made; samples were adjusted to pH 7, pepstatin-A and aprotinin were added, and samples were extracted with acetone to determine SLI by radioimmunoassay. Pentagastrin and sham feeding significantly increased gastric luminal SLI secretion, which appeared to correlate with the increases in volume and acid output. Atropine at 7 micrograms/kg significantly suppressed gastric volume, acid, and SLI outputs stimulated by sham feeding; however, responses to pentagastrin stimulation remained unchanged. To conclude, the cholinergic mechanism regulates gastric intraluminal SLI response to sham feeding but not to pentagastrin infusion.     

CCK receptor antagonism by loxiglumide and gall bladder contractions in response to cholecystokinin, sham feeding and ordinary feeding in man.

The postprandial contractions of the gall bladder result from the interaction of neurohormonal factors but their relative contribution is unknown. This study was designed to determine the role of cholecystokinin (CCK) in gall bladder contractions using a highly selective and potent CCK-receptor antagonist, CR-1505 (loxiglumide) in healthy men either infused with exogenous CCK in graded doses (1.56-50 pmol/kg/h) or subjected to modified sham feeding (MSF) and ordinary feeding tests. The gall bladder volume measured by real time ultrasonography showed dose dependent decrease in the gall bladder volume in 10 subjects when CCK8 was infused iv in graded doses reaching about 15% at 1.56 pmol/kg/h and 91% at 50 pmol/kg/h. Close correlation between the decrease in gall bladder volume and the dosage of CCK or the increments in plasma CCK-bioactivity was observed. After pretreatment with loxiglumide, CCK resulted in similar increments in plasma CCK-bioactivity but failed to affect the gall bladder volume at CCK doses up to 6.25 pmol/kg/h and caused only 53% reduction at 50 pmol/kg/h. Modified sham feeding and real feeding reduced the volume of gall bladder by 20% and 70%, respectively and loxiglumide decreased these values to 15% and 30%, respectively. This study provides evidence that loxiglumide is highly potent and selective CCK antagonist and that endogenous CCK plays an important role both in the postprandial contractions of gall bladder.     

Hyperglycemia reduces pancreaticobiliary secretion in response to modified sham feeding in humans

BACKGROUND/AIMS: We have investigated the effect of acute hyperglycemia on pancreaticobiliary secretion and pancreatic polypeptide (PP) release. METHODS: Duodenal outputs of bilirubin, trypsin, lipase, amylase and bicarbonate were measured using a recovery marker under basal conditions and in response to modified sham feeding (MSF) in 6 healthy subjects on two separate occasions: during normoglycemia and during acute hyperglycemia (15 mmol/l). RESULTS: During hyperglycemia the basal pancreaticobiliary output was significantly (p < 0.05) reduced. During normoglycemia MSF significantly (p < 0.05) increased the output of bilirubin and pancreatic enzymes; during hyperglycemia only the output of pancreatic enzymes increased significantly (p < 0.05) over basal. During MSF the outputs of bilirubin (16 +/- 4 vs. 4 +/- 2 micromol/30 min), trypsin (26 +/- 7 vs. 7 +/- 4 U/30 min), lipase (36 +/- 11 vs. 15 +/- 6 kU/30 min), amylase (3.4 +/- 0.7 vs. 1.4 +/- 0.7 kU/30 min) and bicarbonate (0.8 +/- 0.1 vs. 0.5 +/- 0.1 mmol/30 min) were significantly (p < 0.05) reduced during hyperglycemia compared to normoglycemia. During hyperglycemia basal and MSF-stimulated PP levels were significantly (p < 0.05) reduced compared to normoglycemia. MSF did not significantly influence plasma cholecystokinin levels in both experiments. CONCLUSIONS: This study indicates (1) that the blood glucose levels affect basal and cephalic stimulated pancreaticobiliary secretion and (2) that the PP secretion during hyperglycemia is reduced, suggesting impaired vagal cholinergic activity during hyperglycemia.     

Cephalic phase of pancreatic-polypeptide secretion studied by sham feeding in man.

The effect of sham feeding on pancreatic-polypeptide (PP) secretion was studied in 26 duodenal ulcer (DU) patients and in 8 healthy subjects. Modified sham feeding (MSF) by the 'chew and spit' technique induced a rapid increase in plasma concentrations of PP both in DU patients, 56 (2-138) pmol/l, and in the healthy subjects, 24 (2-45) pmol/l, median peak-increment and range. Four out of 26 DU patients and 2 out of 8 healthy subjects did not show any PP response to MSF. The PP response to MSF was abolished by pretreatment with atropine, or benzilonium, a quarternary anti-muscarinic agent with minimal cerebral actions. The PP response to MSF was not dependent on the gastric acid response, since a PP response to sham feeding was found in 13 out of 17 patients with selectively denervated parietal cell area, and thus, without acid response. During adequate sham feeding, in which the food is also swallowed but does not reach the stomach, the PP increment, 100 (81-129) pmol/l, was larger than during MSF in the same patients, 51 (8-78) pmol/l, median and total range, P less than 0.05, N = 7. No correlation was found between the PP and acid responses to sham feeding. It is concluded that cephalic stimulation provoked by tasting, chewing and swallowing is a major stimulus in the initial, rapid PP response during a meal; and that the PP cells are probably stimulated directly by a cholinergic mechanism.     

Pancreatic polypeptide response in patients with chronic pancreatitis

We studied the plasma pancreatic polypeptide (PP) response to a meal in patients with pancreatitis and attempted to correlate the PP increment with the degree of pancreatic exocrine insufficiency. Control subjects and patients with recurrent pancreatitis showed significant mean increase (P<0.05) in plasma PP concentration in response to food. By contrast chronic pancreatitis patients had no significant increase in plasma PP. However, some subjects with normal pancreatic secretion had no response and some patients with chronic pancreatitis did show a response. In addition, no correlation was observed between the PP response and pancreatic exocrine secretion. We conclude that the PP response to a meal has only limited value in the detection of pancreatic destruction.     

Pancreatic polypeptide response to food and cerulein in patients with total gastrectomy

In order to investigate the intestinal phase of pancreatic polypeptide (PP) release, the hormonal response to food and cerulein was measured in 19 patients with truncal vagotomy and total gastrectomy (10 with simple esophagojejunal anastomosis and 9 with an additional duodenojejunal anastomosis) and in 7 healthy subjects. After gastrectomy, the early peak of the physiologic biphasic PP response to food was lost but the late predominant phase was unchanged so that the overall postprandial release of the hormone was not significantly lowered. Gastrectomized patients with duodenal bypass had postprandial serum levels only slightly lower than those of patients with preserved duodenal transit of food. Serum PP response to cerulein stimulation was significantly lower in vagotomized patients than in healthy subjects. However, in operated patients as well as in controls, cerulein infusion did induce a rapid increase of plasma PP, followed by persistently elevated levels. The PP response to cerulein was abolished by atropine pretreatment. Our findings indicate that the intestinal phase of meal-stimulated PP response is not dependent on the integrity of vagal pancreatic innervation and that the preservation of the duodenal transit of food after total gastrectomy is not crucial for the maintenance of the enteroinsular axis.     

Effect of an opiate antagonist (naloxone) on the gastric acid secretory response to sham feeding,pentagastrin, and histamine in man

We studied the effect of the opiate antagonist naloxone on the human gastric acid secretory response to three secretory stimulants: sham feeding, pentagastrin, and histamine. Intravenous naloxone (40 g/kg/hr) significantly inhibited the acid secretory response to sham feeding without affecting the serum gastrin response to sham feeding. Naloxone also significantly reduced pentagastrin- and histamine-stimulated acid secretion. These studies indicate that naloxone reduces acid secretion in response to all stimulants of acid secretion yet tested in humans.This study was supported by grants AM-16816 and AM-17328, from the National Institute of Arthritis, Metabolism and Digestive Diseases.Presented in part at the Plenary Session of the American Gastroenterological Association, Salt Lake City, Utah, May 19, 1980.     

Rectosigmoid motility response to sham feeding in irritable bowel syndrome. Evidence of a cephalic phase

Rectosigmoid pressure recordings by means of open-ended perfused catheters were performed on 21 patients with the irritable bowel syndrome (IBS). Motility indexes were calculated in resting conditions, after sham feeding, after a meal, and after 0.5 mg neostigmine intravenously. Each step of stimulation caused a significantly increased motility index compared with the previous step (p less than 0.01). The increase in rectosigmoid pressure activity after sham feeding indicates the existence of a cephalic phase in the postprandial motor response of the colon in IBS.     

Gastric acid and pancreatic polypeptide responses to modified sham feeding. Effects of truncal and parietal cell vagotomy.

The effects of truncal vagotomy and parietal cell vagotomy on gastric acid secretion and plasma gastrin and pancreatic polypeptide release were studied in 28 duodenal ulcer patients under basal conditions and after modified sham feeding and infusion of pentagastrin (2 micrograms/kg/h). Before vagotomy gastric acid output in response to modified sham feeding was significantly higher than basal acid secretion in all subjects tested and reached about 45% of the pentagastrin maximum. No difference in the increase in acid response, or in the pancreatic polypeptide response to modified sham feeding was found between patients with high and low basal secretion. Plasma gastrin concentration was unaltered by modified sham feeding before and after truncal vagotomy or parietal cell vagotomy, although after vagotomy it tended to reach higher values than before this procedure. After truncal vagotomy, basal pancreatic polypeptide concentration was decreased and modified sham feeding-induced pancreatic polypeptide increment was completely eliminated. Four weeks after parietal cell vagotomy, the modified sham feeding-induced increment in plasma pancreatic polypeptide was significantly decreased and observed only in seven of 12 patients. Four to five years after parietal cell vagotomy all subjects responded to modified sham feeding with pancreatic polypeptide increment similar to that before vagotomy and in three of 12 patients acid response to modified sham feeding was seen. This study indicates that truncal vagotomy eliminates gastric acid and plasma pancreatic polypeptide responses to vagal excitation while parietal cell vagotomy abolishes gastric acid response and reduces temporarily the pancreatic polypeptide response to modified sham feeding (possibly because of transient impairment of the vagal innervation of the pancreas). (2) A high ratio of basal to maximal acid output in non-operated duodenal ulcer patients is not associated with a low acid response to modified sham feeding, nor with a high pancreatic polypeptide concentration, and (3) Restitution of the pancreatic polypeptide response to modified sham feeding five years after parietal cell vagotomy does not indication ineffective denervation of the parietal cells.     

Pancreatic polypeptide response to a protein-rich meal in diabetic patients with and without neuropathy

A protein-rich meal and insulin-induced hypoglycemia (ITT) are two of the most important stimuli on pancreatic polypeptide (PP) secretion in diabetic patients. Previous studies have shown a reduced PP response to ITT in diabetic patients with autonomic neuropathy (AN). Twelve patients without AN (mean age 44 +/- 10.8 yr, mean duration of diabetes 11 +/- 5.6 yr), 9 with AN (51.4 +/- 6 yr, 15.8 +/- 6.9 yr) and 9 controls (N) were studied. AN was assessed by the evaluation of the beat-to-beat variation of the heart rate during deep breathing. PP secretion was stimulated by a protein-rich meal (200 g meat, 150 g milk). All insulin-dependent diabetic (IDD) patients lacked circulating PP antibodies. All diabetic patients showed a significant reduction in the early vagal phase compared to controls. This behavior was more evident in diabetic patients with AN and the secondary phase of these two groups overlapped with the response of controls. These data may be explained by the initial alterations of vagal functions not detectable by current methods.     

Pancreatic polypeptide secretion

Pancreatic polypeptide, a 36-amino peptide, is released from the pancreas by a variety of stimuli, including intravenous Boots secretin. Studies in a generalized destructive and inflammatory process such as chronic pancreatitis have revealed a markedly diminished response to stimulation. To assess whether pancreatic polypeptide release in response to Boots secretin provides a useful measure of pancreatic destruction in cystic fibrosis, 41 patients with proven cystic fibrosis, aged 14 months-23 years, and seven control subjects, aged 18–24 years were studied. Serum pancreatic polypeptide, measured by radio-immunoassay, rose from a basal of 18.5±2.7 pmol/liter to a peak of 35.6±4.3 pmol/liter at 5 min in cystic fibrosis, and from a basal of 10.8±2.7 pmol/liter to a 5-min peak of 109±27.7 pmol/liter in control subjects. The basal levels of both groups were similar but the cystic fibrosis patients had a significantly lower peak response than controls (P<0.05). The peak over basal pancreatic polypeptide ratio was calculated and was less than five in 93% of cystic fibrosis patients, whereas all control subjects had a ratio greater than five. Pancreatic polypeptide measurements in response to secretin, may be a convenient and useful means of following the course of pancreatic disease in a chronic illness such as cystic fibrosis.