Basal Pancreatic Polypeptide Levels Research Articles

Absence of cardiovascular autonomic dysfunction and vagal pancreatic impairment in idiopathic achalasia of the oesophagus

Extra-oesophageal autonomic dysfunction in idiopathic achalasia is not well documented, due to contradictory results reported. We aimed to study the cardiovascular and pancreatic autonomic function in patients with idiopathic achalasia. Thirty patients with idiopathic achalasia (16M/14F; 34.5 +/- 10.8 years) and 30 healthy volunteers (13M/17F; 34.8 +/- 10.7 years) were prospectively studied. Age >60 years and conditions affecting results of autonomic evaluation were excluded. Both groups underwent the sham feeding test and plasmatic levels of pancreatic polypeptide (PP) were determined by radioimmunoassay (basal, at 5, 10, 20 and 30 min). Cardiovascular parasympathetic (deep breathing, standing, Valsalva) and sympathetic function (postural decrease of systolic blood pressure, Handgrip test) were assessed. Statistical comparison of basal and increase levels of PP and parasympathetic/sympathetic cardiovascular parameters was performed between groups. Basal levels of PP were similar in controls and patients and maximum increase of PP during sham feeding test. A similar rate of abnormal cardiovascular tests was found between groups (P > 0.05). E/I ratio was the mostly impaired parameter (patients: 36.7% vs controls: 20%, P = 0.15, chi-squared test). Autonomic cardiovascular tests and pancreatic response to vagal stimulus are not impaired in patients with primary achalasia of the oesophagus.

A safe and noninvasive test for vagal integrity revisited.

Measurement of pancreatic polypeptide (PP) response to sham feeding and pharmacological stimulation is a safe, noninvasive, and sensitive test for vagal integrity. Interventional study with control arms. Tertiary center for esophageal surgery. Thirty healthy volunteers and 25 patients who underwent total esophagectomy formed the control group with intact vagi and known vagotomy, respectively. Blood samples were obtained 15 minutes before and immediately before sham feeding to determine basal PP levels. Samples were also obtained 15, 30, 45, and 60 minutes after the sham feeding and 10 and 20 minutes after administration of 5 mg of intravenous edrophonium hydrochloride. Pancreatic polypeptide response to sham feeding and edrophonium administration were compared in both groups and the optimal percentage of rise from basal levels with maximal sensitivity and specificity was determined. Basal levels were similar in both groups (50 vs 45 ng/L). The maximum percentage of rise within 30 minutes after sham feeding was significantly higher in healthy subjects than in patients who underwent vagotomy (P<.001). A rise of 50% was seen in 24 (83%) of the 29 healthy subjects vs 2 (8%) of the 25 patients who underwent vagotomy (P<.001). This rise in PP level had a sensitivity of 83%, specificity of 92%, and a positive predictive value of 92% for identifying an intact vagus. The administration of endrophonium did not improve these results. A rise of more than 50% in the PP level within 30 minutes of sham feeding is a strong indicator of vagal integrity. This test has the potential to investigate vagal injury after gastroesophageal surgery.

The effect of exclusive parenteral nutrition, constant rate enteral nutrition, partial meal feeding, normal oral feeding and etiology on the plasma pancreatic polypeptide levels in children

Plasma pancreatic polypeptide (PP) levels were determined by radioimmunoassay in 100 children. Of the 81 children on Total Parenteral Nutrition (TPN), 32 were studied after cyclic TPN (cTPN), 66 after Partial Meal Feeding plus Parenteral Nutrition, 25 after Constant Rate Enteral Nutrition and 18 during Normal Oral Feeding. Nineteen controls received normal alimentation. PP levels during TPN (172 ± 17 pg/ml), cTPN (150 ± 23) and Constant Rate Enteral Nutrition (200 ± 27) were similar to each other and to pre-prandium (p), Normal Oral Feeding (198 ± 22) and controls (196 ± 40). PP increased (p < 0.05) in post-prandium (pp), Partial Meal Feeding (233 ± 23) compared to TPN, cTPN, p Normal Oral Feeding and p controls, but remained at half that of pp Normal Oral Feeding (387 ± 58) and pp controls (410 ± 91, p < 0.001). The p PP levels were significantly reduced in chronic intestinal pseudo-obstruction (CIPO) (90 ± 22, p < 0.02) and short bowel (length < 100 cm) (76 ± 17, p < 0.001), as compared to controls. This study indicates that TPN or Constant Rate Enteral Nutrition do not modify basal PP levels. Normal Oral Feeding and Partial Meal Feeding produce a significant pp stimulation of PP release. Intestinal pathology can interfere with p plasma PP levels.

The regulation of basal pancreatic polypeptide levels in dogs

In response to to various stimuli, pancreatic polypeptide (PP) release is predominantly mediated by cholinergic mechanisms, and may be modulated by sympathetic and opiate (inhibitory) effects. However, the mechanisms regulating basal PP levels remain unclear. We examined the possible role of the sympathetic nervous system and endogenous opiates in the regulation of basal levels of pancreatic polypeptide in trained conscious dogs. During prolonged (150 min) α- or β-adrenergic blockade with phentolamine and propranolol, separately or in combination, there was no change in the basal PP levels of 154 ± 20 pg/ml . Effective adrenergic modulation of pancreatic hormones was evident since α blockade led to a rise in insulin and glucagon, β blockade led to a fall in insulin and glucagon, while combined α- and β-adrenergic blockade did not affect insulin or glucagon. Opiate blockade with naloxone (1.25 mg followed by 1 μg/kg/min) led to a delayed fall in PP from 153 ± 22 to 89 ± 15 pg/ml at 90 min (no change by 30 min), without a change of insulin or glucagon. Infusion of a potent morphine analogue d-Met 2-Pro 5-enkephalinamide (0.5 μg/kg/min) led to a sustained fall in PP to 91 ± 8 pg/ml by 30 min without a change in insulin or glucagon. Somatostatin infusion (0.2 μg/kg/min) with insulin and glucagon replacement, led to a similar sustained fall in PP. It is concluded that in dogs: (1) in contrast to insulin and glucagon, at basal conditions the plasma level of PP is not modulated by endogenous α- or β-adrenergic influences; (2) opiate tone does not appear to be involved in the maintenance of basal PP levels; the delayed suppression by high-dose naloxone most likely represents a naloxone agonist effect; (3) the mechanism of the opiate (and high dose naloxone) inhibitory effect is probably not mediated by somatostatin, since insulin and glucagon were unaffected.

Pentobarbital suppresses basal and reflexive pancreatic polypeptide release in dogs.

We sought to determine in overnight-fasted dogs whether basal or 2-deoxy-D-glucose (2-DG)-stimulated levels of pancreatic polypeptide (PP) could be reliably used as an index of cholinergic activity at the pancreas and thereby determine the effect of pentobarbital anesthesia on this cholinergic outflow. At low basal PP levels, either atropine or pentobarbital had a small effect on PP levels; at higher basal levels, both atropine and pentobarbital had a larger effect. Thus both drugs decreased PP in proportion to its initial basal level, suggesting that basal PP levels have a variable cholinergic component. Atropine abolished the PP response to intravenous 2-DG, confirming in our animal model that the PP response to neuroglucopenia is entirely cholinergically mediated. Pentobarbital also abolished the PP response to 2-DG, suggesting that anesthesia either suppresses cholinergic outflow to the pancreas or the response of the pancreatic F-cell to it. To test the latter hypothesis, the acetylcholine analogue bethanechol was administered before and during pentobarbital anesthesia. The PP response to direct cholinergic stimulation was not abolished by pentobarbital, although it was reduced modestly. We conclude that only part of the basal level of PP is under cholinergic control; all of the PP response to 2-DG is cholinergically mediated; pentobarbital anesthesia abolishes the cholinergic input to the pancreas; and if the endogenous cholinergic input influences certain pancreatic endocrine and exocrine responses, then its contribution would be seriously underestimated when studied in pentobarbital-anesthetized animals.

Elevated serum levels of pancreatic polypeptide are related to impaired glucose handling in inflammatory states.

Glucose handling and insulin secretion were studied in patients with inflammatory connective tissue diseases and correlated to circulating levels of immunoreactive pancreatic polypeptide (PP). The patients had normal fasting serum levels of insulin and normal insulin response to intravenous glucose loading. Ten of 16 patients had an impaired glucose tolerance, defined as a K rate of less than one. The basal PP levels, which were elevated in half of the patients, were inversely correlated to the K values but showed no relationship to basal or maximum insulin levels. The degree of the impaired glucose handling in the patients was related to the degree of the inflammatory activity as defined by acute-phase reactants. Elevated PP levels may be partly responsible for impaired glucose tolerance in inflammatory states either as an inhibitor of peripheral insulin activity or as an inhibitor of hypersecretion of insulin, needed to overcome decreased tissue sensitivity for insulin.

Effect of opiate-active substances on pancreatic polypeptide levels in dogs

The present study examines the effect of orally and intravenously administered opiate-active substances on peripheral vein plasma pancreatic polypeptide (PP) levels in conscious dogs. The intragastric instillation of digested gluten stimulated postprandial PP levels significantly which was reduced by the specific opiate-receptor antagonist naloxone. Naloxone had no effect when added to undigested gluten. Similarly, naloxone reduced significantly the postprandial PP response to a test meal of casopeptone which contains the opiate-active β-casomorphins. The addition of synthetic β-casomorphins to a liver extract/sucrose test meal significantly augmented the rise of postprandial PP levels which was also blocked by naloxone. The intravenous infusion of morphine, leu-enkephalin, D-ala 2-D-leu 5-enkephalin, β-casomorphin-5 and β-casomorphin-4 elicited a dose-dependent and naloxone reversible effect on basal PP levels. During a background infusion of glucose and amino acids the same opiate-active substances had either none or a stimulatory effect on PP release in these dogs. The addition of naloxone abolished the stimulatory effect in response to β-casomorphin-5 and β-casomorphin-4 and resulted in an inhibition of PP levels during the infusion of morphine and leu-enkephalin. This latter inhibitory effect was no longer observed when the dose of naloxone was increased ten- and fifty-fold, respectively. The present data suggest that orally ingested opiate-active substances participate in the stimulation of postprandial PP release in dogs via specific opiate-receptor mediated mechanisms. The effect of intravenously administered opiate-active substances on PP levels depends on the metabolic state with regard to the level of circulating nutrients. It is suggested that PP release is stimulated via μ-opiate receptors and inhibited via δ-opiate receptors. An increase of circulating nutrients would “activate” μ-receptor sites which are masked in the basal state when exogenous opiates are administered. However, with regard to endogenous opiates an increase of circulating nutrients, mainly carbohydrates, activates inhibitory effects of endogenous opiates suggesting that exogenous and endogenous opiates act at different target sites.

ABNORMAL PANCREATIC POLYPEPTIDE RESPONSE TO INTRAVENOUS GLUCOSE IN URAEMICS. A POSSIBLE MECHANISM BEHIND IMPAIRED GLUCOSE TOLERANCE IN URAEMIA

Glucose handling and insulin secretion were studied in chronic haemodialysis patients and correlated with circulating levels of immunoreactive pancreatic polypeptide (PP). No correlation was found between the elevated basal levels of PP and K-rate or the maximum insulin response after a single intravenous injection of glucose. Fifty-three per cent of the patients had a normal glucose tolerance defined as a K-rate more than 1. This group of uraemics had a tendency to an exaggerated insulin response compared with the controls but no significant changes of serum-PP levels after a glucose stimulus were observed. In contrast, uraemic patients with a K-rate less than 1 and normal insulin response, showed significant increases of serum-PP at 4 and 6 min after glucose administration. Among all uraemic patients we found a significant inverse correlation between the K-rate and the early PP response (P less than 0.05) and a significant positive correlation between the K-rate and early insulin response (P less than 0.05). PP release in response to acute hyperglycaemia may be one mechanism behind impaired glucose handling in uraemics, either by reducing peripheral insulin activity or by preventing insulin secretion sufficient to overcome the decreased tissue sensitivity to insulin.

Plasma human pancreatic polypeptide response in chronic pancreatitis.

The changes of plasma pancreatic polypeptide (PP) and the relationship between PP response and exocrine pancreatic function in chronic pancreatitis are reported. In 260 healthy control subjects, plasma PP levels increased gradually with aging. Basal levels of PP in 30 patients with chronic pancreatitis were significantly lowered in comparison with age matched control subjects (control 95.0 +/- 10.3 pg/ml, chronic non-calcifying pancreatitis 45.0 +/- 7.3 pg/ml, chronic calcifying pancreatitis 40.4 +/- 6.0 pg/ml). Plasma PP response by insulin induced hypoglycemia, test meal ingestion, and pancreozymin-secretion represented a significant decrease in patients with chronic pancreatitis. Additionally, maximum PP response, especially in pancreozymin-secretin injection, had a good correlation with exocrine pancreatic function. These results suggest that the determination of plasma PP response is useful for the diagnosis of chronic pancreatitis.

Evidence for an intestinal mechanism of pancreatic polypeptide release.

The purpose of this study was to define the existence of an intestinal phase of pancreatic polypeptide (PP) release and to assess whether it was mediated by a cholinergic-sensitive mechanism. Four conscious dogs with 20-cm upper intestinal Thiry-Vella loops and chronic gastric fistulas were used. The Thiry-Vella (T-V) loops were perfused with 10% liver extract or 0.154 M NaCl at a rate of 1 ml/min for 120 min. In a separate experiment, 240 ml of 10% liver extract was infused over a 5-min period into the stomach via the gastric fistula. Basal PP levels were 29 +/- 4 fmol/ml. The gastric infusion of liver extract caused a significant increase of plasma PP levels to a peak of 215 +/- 29 fmol/ml (P less than 0.05). The perfusion of the T-V loop with liver extract significantly increased plasma PP levels over basal to a peak of 73 +/- 14 fmol/ml (P less than 0.05). This value was significantly less than that released by gastric infusion of liver extract (P less than 0.05). Perfusion of the loop with NaCl did not significantly alter basal plasma PP levels (P greater than 0.05). PP release by perfusion of the T-V loop with liver extract was abolished by atropine intravenous bolus (0.2 mg/kg). Although the combination of bethanechol (100 microgram/kg/hr intravenous) and liver extract consistently increased the plasma levels of PP, the values did not attain statistical significance when compared to liver extract alone (P greater than 0.05). The data presented are thus consistent with the hypothesis that there is an enteric phase of pancreatic polypeptide release and that this enteropancreatic reflex is mediated by a cholinergic-sensitive mechanism which might be hormonal or neural.

Effect of truncal vagotomy on pancreatic polypeptide response after intravenous glucose administration

Intravenous glucose infusion was performed in six dogs with and without truncal vagotomy, and plasma pancreatic polypeptide (PP) responses were compared before and after truncal vagotomy. Following truncal vagotomy, basal PP levels decreased significantly from 286 ± 64 pg/ml (mean ± S.E.) to 94 ± 14 pg/ml ( P < 0.05). Basal plasma insulin and blood glucose levels also tended to be lower, but not significantly. During the influsion of glucose, blood glucose concentrations rose rapidly in both groups and after 15 min reached peak values which were not significantly different from each other. In the vagotomized group the plasma insulin response to intravenous glucose infusion was significantly lower than in the control group. Following intravenous glucose loading, plasma PP concentrations decreased rapidly in both groups, but the PP level in the vagotomized group was suppressed only to 77 ± 4% of the basal level whereas in the control group it decreased to 45 ± 8%, significantly lower than in the vagotomized group ( P < 0.01). These results suggest that basal PP is regulated by vagal tonus and that vagus controls, at least in part, suppression by intravenous glucose administration.

Variable effect of lithium on canine pancreatic polypeptide and gastrin release by a meal or bombesin.

Lithium is a cation which has central nervous system effects and is able to interfere with both the release and action of polypeptide hormones. We examined its effect on basal and stimulated plasma gastrin and pancreatic polypeptide (PP) levels in 4 dogs with chronic gastric fistulas. Gastrin and PP release were stimulated by a meal or bombesin nonapeptide infusion (1.2 microgram kg-1h-1). The studies were repeated 24h and 14 days after lithium administration (600 mg/12 h) orally. Basal plasma lithium values were undetectable and rose to 0.9 /+- 0.2 mmol l-1 in the acute and 1.0 +/- 0.2 mmol l-1 in the chronically treated animals. The dogs did not have any discernible side effects. Basal plasma gastrin was 14 +/- 4 fmol ml -1 and was not significantly altered by either 1 or 14 days Li+( p greater than 0.05). Gastrin release stimulated by either a meal or bombesin was not significantly decreased by acute or chronic Li+ administration . Acute lithium administration produced a slight but significant increase in meal-stimulated gastrin (p less than 0.01). Neither acute nor chronic lithium administration altered bombesin stimulated gastric acid secretin (p greater than 0.05). Basal PP levels were 24 +/- 7 fmol ml-1 and not significantly altered by 1 or 14 days Li+ administration. Both acute and chronic Li+ inhibited PP release by bombesin in the first 30-min period of the study (p less than 0.01). 14 days Li+ significantly inhibited both first and second hour PP responses to a meal (p less than 0.01). The mechanism of the cationic modification of the release of pancreatic polypeptide requires further elucidation.

Pancreatic polypeptide. Release following surgery for duodenal ulcer disease.

The pancreatic polypeptide (PP) response to food has been measured by radioimmunoassay in patients with duodenal ulcer and 3 months following proximal gastric vagotomy (PGV), 18 and 49 months following truncal vagotomy and pyloroplasty (TV), 35 months following Billroth II gastrectomy (BII), and 35 months following truncal vagotomy and antrectomy (TV&A). Basal PP levels and those in response to food were similar in DU and PGV, but these values were significantly higher than those 18 months or 49 months after TV, or after BII and TV&A. The responses in the latter four groups were similar and in particular, the levels 18 and 49 months after TV were the same. These results indicate that the release of PP by food in unoperated patients consists of two phases, a primary phase which requires both intact vagi and an intact stomach and a secondary phase which also depends on vagal innervation and normal gastric anatomy. Disturbances in vagal innervation or gastric integrity lead to profound changes in PP release which may be due to interruption of neural arcs or loss of gastric hormones. Unlike others, we have been unable to document a return of PP secretion towards normality with time after TV.