Plasma Pancreatic Polypeptide Levels Research Articles

Central but not peripheral glucocorticoid infusion in adrenalectomized male rats increases basal and substrate-induced insulinemia through a parasympathetic pathway.

Glucocorticoids acting through the central nervous system are postulated to play a role in the hyperinsulinemia and increased adiposity of obesity. We investigated the role of parasympathetic activation in glucocorticoid-induced hyperinsulinemia. Plasma pancreatic polypeptide (PP) levels were used as an index of parasympathetic output. Insulinemia and plasma PP levels were measured basally and after intravenous glucose injection (300 mg/kg) in adrenalectomized male rats infused with dexamethasone (7.5 microg/kg per day) intracerebroventricularly (ICV) or subcutaneously (SC) for 3 to 6 days in the presence or absence of acute atropine blockade (1.0 mg/kg). Food intake was controlled between groups. Compared with normal rats, adrenalectomy decreased white adipose tissue depot weights and leptinemia, and these were restored to normal values by ICV but not SC dexamethasone infusion. Adrenalectomy significantly reduced insulinemia below normal levels, which was restored by SC dexamethasone replacement. However, ICV dexamethasone replacement increased insulinemia of adrenalectomized rats to levels higher than normal control values (basal, 500 +/- 40 pM vs. 280 +/- 40 pM; 1-minute postglucose, 2500 +/- 180 pM vs. 1240 +/- 260 pM; p < 0.0001) and increased plasma PP levels, which were correlated with insulinemia. Atropine significantly reduced plasma insulin and PP to levels similar to normal controls but had no effect in any other group. These data show that glucocorticoids act within the brain to increase insulinemia, most likely through activation of parasympathetic efferent fibers. Such an affect would contribute to the adipogenic effects of central glucocorticoids.

Role of Pancreatic Polypeptide as a Market of Transplanted Insulin-Producing Fetal Pig Cells

Transplantation of insulin-producing fetal pancreatic tissue into diabetic recipients has been shown to normalize blood glucose levels after several months. This time period is required for the growth and maturation of the fetal tissue so insulin levels cannot be used as a marker of graft function while the beta-cell is immature. Therefore, we have examined the use of another pancreatic endocrine hormone, pancreatic polypeptide (PP), to monitor graft function. The cell that produces this hormone has been shown to be the first mature endocrine cell in the fetal pancreas. Fetal pig pancreatic tissue, both in the form of 1 mm3 explants and islet-like cell clusters (ICCs), was transplanted into immunodeficient SCID mice and the levels of PP and insulin were measured in plasma and in the graft for up to 12 weeks. PP was detected in the untransplanted explants (0.58 pmol/mg) and ICCs (0.06 pmol/ICC) and the PP to insulin ratio was 2.7% and 5.8%, respectively. PP (but not porcine C-peptide, a marker of insulin secretion) was detectable in the plasma of SCID mice from 4 days to 3 weeks after transplantation, but not thereafter. The highest values were obtained at 4 days to 1 week. In the grafted tissue PP and insulin were present at all time points and the ratio of PP to insulin was 59%, 87%, 75%, 56%, 7%, 8%, and 7% at 4 days, 1, 2, 3, 6, 9, and 12 weeks, respectively. The decline in PP levels 3 weeks after transplantation was associated with beta-cell development in the graft. PP was also secreted by fetal pig pancreatic explants transplanted into diabetic NOD/SCID mice, with plasma levels measurable in the first week after the tissue was grafted. In immunocompetent BALB/c mice transplanted with the tissue, PP was detectable in plasma for 2 days after transplantation but not at 4 days, when cellular rejection commenced, or thereafter. We conclude that plasma PP levels can be used as a marker of the viability of fetal porcine pancreatic tissue in the first 3 weeks after it is transplanted into mice. These findings may have relevance to fetal pancreatic tissue transplanted into humans if suitable techniques can be developed to separate pig from human PP.

Effects of glucagon-like peptide-1(7-36)amide on antro-pyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans

BACKGROUNDGlucagon-like peptide-1(7-36)amide (GLP-1) is a gut hormone released postprandially. Synthetic GLP-1 strongly inhibits gastric emptying in healthy subjects and in patients with diabetes mellitus.AIMSTo investigate the effects of GLP-1 on...

Plasma pancreatic polypeptide response to secretin.

Intravenously administered secretin stimulates pancreatic polypeptide (PP) release in patients with endocrine enteropancreatic tumors, but data in patients with nontumorous disorders are controversial. Therefore, we aimed to evaluate the plasma PP pattern after secretin administration in healthy subjects and in patients with gastroduodenal diseases investigated for recurrent ulcer disease and/or hypergastrinemia. Synthetic secretin was given as an intravenous bolus (2U/kg) in ten patients with Zollinger Ellison syndrome, ten with duodenal ulcer, ten with atropic gastritis and ten healthy volunteers. Blood samples were taken before and at regular intervals for 30min after secretin injection. Plasma PP and gastrin levels were measured by radioimmunoassay. Secretin promptly and significantly (P<0.01) increased PP plasma levels in all groups of subjects without any differences in peak values. There were no significant correlations between PP and gastrin plasma levels. Secretin at pharmacological doses is a powerful stimulus for PP release.

Effect of intraduodenal bile salt on pancreaticobiliary responses to bombesin and to cholecystokinin in humans.

Bile salts modulate postprandial gallbladder emptying and pancreatic enzyme secretion, possibly by interfering with plasma cholecystokinin (CCK) responses. The regulatory role of bile salts in the absence of nutrients from the gut is poorly understood. Therefore, we studied the effect of intraduodenal sodium chenodeoxycholate on bombesin (BBS)- or CCK-stimulated plasma CCK levels, plasma pancreatic polypeptide levels, gallbladder motility, and pancreatic enzyme secretion. In a crossover design, saline without or with chenodeoxycholate was perfused intraduodenally for 3 hours in healthy volunteers. During the last hour, either BBS (n = 9) or CCK (n = 10) was infused intravenously. Chenodeoxycholate inhibited BBS-stimulated gallbladder emptying from 59% +/- 4% to 34% +/- 6% (P <.05) and intraduodenal bilirubin output from 41 +/- 9 to 21 +/- 5 micromol/h (P <.05), but it increased integrated plasma CCK levels from 157 +/- 19 to 184 +/- 19 pmol/L. 60 min (P =.01). Similarly, chenodeoxycholate administration inhibited gallbladder emptying and bilirubin output in response to intravenous CCK. Chenodeoxycholate also tended to reduce pancreatic polypeptide release and intraduodenal amylase output in response to intravenous BBS or CCK. It is concluded that intraduodenal chenodeoxycholate administration inhibits BBS- or CCK-stimulated gallbladder emptying, probably by diminishing target organ sensitivity to circulating CCK.

Altered vagal and intestinal mechanosensory function in chronic unexplained dyspepsia

Background—Abnormal visceral mechanosensory and vagal function may play a role in the development of functional gastrointestinal disorders.Aims—To assess whether vagal efferent and afferent function is linked with small intestinal mechanosensory...

Leptin—A regulator of islet function?: Its plasma levels correlate with glucagon and insulin secretion in healthy women

It has previously been demonstrated that plasma leptin correlates to body fat content. It has also been demonstrated that in subjects with normal glucose tolerance, circulating leptin correlates to circulating insulin and to insulin secretion and that these relations are independent of body fat. However, whether leptin also covaries with other islet hormones is not known. We therefore studied the relation between plasma levels of leptin and glucagon secretion and circulating pancreatic polypeptide (PP) in healthy humans. Arginine was injected intravenously (5 g) at fasting and at 14 and 28 mmol/L glucose in 71 postmenopausal women with normal glucose tolerance. In a multivariate analysis controlling for the influence of the body mass index, we found that circulating leptin correlated significantly to fasting insulin (r = .38, P = .002), and to circulating insulin at 14 mmol/L glucose (r = .29, P = .0019) and 28 mmol/L glucose (r = .32, P = .009), as well as to the insulin response to arginine at all three glucose levels (r > .30, P < .013). Circulating leptin, independently of the body mass index, also correlated to fasting glucagon (r = .31, P = .012) and to the glucagon response to arginine at all three glucose levels (r > .28, P < .038). In contrast, circulating leptin did not correlate to plasma glucagon at 14 or 28 mmol/L glucose or to plasma levels of PP. We conclude that circulating leptin correlates to the secretory capacity of both glucagon and insulin but not to the reduction of plasma glucagon during hyperglycemia or to PP in a large group of postmenopausal women. This suggests that islet function is related to circulating leptin in humans.

Effect of duodenum-preserving resection of the head of the pancreas on endocrine and exocrine pancreatic function in patients with chronic pancreatitis

Chronic pancreatitis leads to progressive destruction of pancreatic parenchyma affecting exocrine and endocrine function. We prospectively evaluated the effect of duodenum-preserving resection of the head of the pancreas on pancreatic function. Exocrine and endocrine function were measured in a combined test including (1) urinary PABA recovery; (2) plasma glucose, glucagon, and C-peptide responses; and (3) plasma pancreatic polypeptide response. Nineteen patients were included. Compared with the preoperative state, plasma glucose levels did not increase postoperatively. Plasma C-peptide levels were reduced postoperatively but the difference was not significant. The percentage of insulin-dependent patients did not increase after operation (32% versus 32%). Glucose tolerance improved in 4 patients and deteriorated in 3 patients. Postoperative basal and-meal stimulated plasma pancreatic polypeptide levels were significantly reduced. Postoperative urinary PABA recovery was not significantly different from preoperative values. Neither exocrine nor endocrine pancreatic function are negatively influenced by duodenum-preserving pancreatic head resection.

Gallbladder emptying and cholecystokinin and pancreatic polypeptide responses to a liquid meal in patients with diabetes mellitus.

To investigate gallbladder motility and its regulation in patients with diabetes mellitus (DM), we examined the gallbladder response to an intraduodenal test meal by measuring the temporal course of plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels. Eighteen patients with type 2 DM and 7 healthy subjects (controls) were enrolled. The gallbladder volume was calculated by the sum-of-cylinders method from ultrasonographic images, and plasma CCK and PP were measured by radioimmunoassays. No significant difference was found in either the gallbladder response or in the CCK response between patients with DM and controls. However, the fasting plasma PP level of patients with DM was more than tenfold higher than that of controls. The integrated PP response (IPPR) of patients with DM to the test meal was 8.3-fold higher than that of controls. When patients with DM were grouped according to whether they had been treated with insulin or not, the fasting plasma PP of patients with DM without insulin treatment was significantly higher than the level in those treated with insulin. These results suggest that overproduction of PP-like immunoreactive substance(s) may occur in patients with DM, but the high plasma PP immunoreactivity does not appear to be related to the fasting gallbladder volume or to gallbladder emptying and filling.

Autonomic Mediation of Glucagon Secretion During Insulin-Induced Hypoglycemia in Rhesus Monkeys

Autonomic activation mediates the majority of the increase of glucagon secretion during insulin-induced hypoglycemia in several species including dogs, mice, and rats. However, the role of the autonomic nervous system to increase glucagon during hypoglycemia in humans remains controversial, and investigations in nonhuman primates have not been previously conducted. The autonomic contribution to glucagon secretion during hypoglycemia in a nonhuman primate was examined by two independent pharmacological approaches. Glucagon responses to clamped insulin-induced hypoglycemia were compared in conscious rhesus monkeys in the presence or absence of ganglionic blockade with trimethaphan, or during combined muscarinic and adrenergic receptor blockade with atropine, propranolol, and tolazoline. Insulin-induced hypoglycemia (plasma glucose = 1.9 +/- 0.1 mmol/l) activated parasympathetic nerves to the pancreas as assessed by increased plasma pancreatic polypeptide (PP) levels (delta = 135.0 +/- 36.8 pmol/l, P < 0.01), produced sympathoadrenal activation as assessed by elevations of plasma epinephrine (EPI) (delta = 22.3 +/- 2.95 nmol/l, P < 0.0005) and norepinephrine (NE) (delta = 3.72 +/- 0.77 mmol/l, P < 0.0025) and increased plasma immunoreactive glucagon (IRG) (delta = 920 +/- 294 ng/l, P < 0.025). Nicotinic ganglionic blockade with trimethaphan prevented parasympathetic (deltaPP = 16.5 +/- 16.3 pmol/l, P < 0.01 vs. control) and sympathoadrenal (deltaEPI = 1.52 +/- 0.98 nmol/l; deltaNE = -0.62 +/- 0.24 mmol/l, both P < 0.0025 vs. control) activation during hypoglycemia and inhibited the IRG response by 70% (delta = 278 +/- 67 ng/l, P < 0.025 vs. control). Combined muscarinic and adrenergic receptor blockade reduced parasympathetic activation (deltaPP = 48.3 +/- 16.3 pmol/l, P < 0.01 vs. control) and inhibited the IRG response by a similar degree to ganglionic blockade (deltaIRG = 284 +/- 60 ng/l, P < 0.025 vs. control). These results demonstrate by two independent pharmacological approaches that autonomic activation makes a substantial contribution to increased glucagon secretion during hypoglycemia of approximately 2.0 mmol/l in a species of nonhuman primate.

Acute administration of human galanin in normal subjects reduces the potentiating effect of pyridostigmine-induced cholinergic enhancement on release of norepinephrine and pancreatic polypeptide.

The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems where it often coexists with catecholamines and acetylcholine. Recently we have reported that human GAL (hGAL) in man depresses the release of norepinephrine (NE) and the responses to both assumption of upright posture and insulin-induced hypoglycemia. To gain an insight into the action of hGAL on sympathetic nervous system activity in man, we investigated the effects of a 60-min infusion (80 pmol/kg/min) of hGAL or saline on the release of NE, epinephrine (E) and pancreatic polypeptide (PP) induced by an acetylcholinesterase inhibitor, pyridostigmine bromide (PD), in nine healthy volunteers. PD (120 mg orally) induced a significant rise in plasma concentrations of NE (1.6 +/- 0.04 vs. 1.08 +/- 0.06 nmol/l), E (0.34 +/ 0.05 vs. 0.12 +/- 0.04 nmol/l) and PP (178.06 +/- 33 vs. 37.57 +/- 7.35 pmol/l), whilst it significantly reduced heart rate (HR; 61 +/- 2 vs. 71 +/- 4 beats/min). Changes in plasma levels of PP were determined as an indirect measure of amplification of endogenous cholinergic activity produced by PD. Administration of hGAL blunted the release of NE and PP evoked by PD. The mean (+/- SEM) area under the curve produced by PD of NE (50.05 +/- 3.97 nmol/l.90 min) and PP (8,692.87 +/- 1,724 pmol/l.90 min) was significantly (p < 0.001) reduced by hGAL infusion (2.65 +/- 1.57 nmol/l.90 min and 248.1 +/- 148 pmol/l.90 min, for NE and PP, respectively). hGAL failed to affect significantly the E release evoked by PD. hGAL was able to enhance HR significantly (104 +/- 5 vs. 69 +/- 3 beats/min), and completely prevented the PD-induced slowing of HR. Both PD and hGAL did not alter supine systolic and diastolic blood pressure. We conclude that hGAL significantly reduces the release of NE and PP stimulated by PD-induced enhancement of cholinergic activity. These findings are consistent with a functional interrelationship between GAL and the cholinergic system in man, and may suggest the participation of a cholinergic pathway in the galaninergic modulation of the autonomic nervous system.

Increased Plasma Levels of Pancreatic Polypeptide and Decreased Plasma Levels of Motilin in Encopretic Children

Abnormalities of hormones affecting gastrointestinal motility have been found in "functional" disorders of the gastrointestinal system in adults. One such disorder of childhood, encopresis, is frequently associated with constipation, the treatment of which often eliminates the soiling. We hypothesized that hormones affecting gastrointestinal motility were different between encopretic patients and matched controls. Ten encopretic patients were matched by age, race, and sex with controls who had no history of encopresis or constipation. After an overnight fast, each child consumed a meal of Ensure, the amount of which was based on body weight. Plasma levels of gastrin, pancreatic polypeptide, cholecystokinin, motilin, thyroxine, estrogen, and insulin were measured 20 and 5 minutes before the meal, and 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180 minutes after the meal. Postprandial levels of pancreatic polypeptide remained consistently higher and peaked earlier (P < .05) for encopretic patients. The motilin response was lower (P < .03) for encopretic children than for controls. We conclude that pancreatic polypeptide and motilin responses to a meal are different in encopretic children than in children in the control group. These gastrointestinal hormone findings may in part explain and/or be the result of the severe constipation that frequently underlies the fecal soiling found in these patients. These findings also suggest the motility of the stomach and small intestine may be abnormal in encopresis.

Effects of cholecystokinin and glucagon-like peptide 1 on the secretion of pancreatic polypeptide in mice

The gut hormones, cholecystokinin (CCK) and truncated glucagon-like peptide 1 (GLP-1(7-36)amide or GLP-1) both stimulate insulin secretion and affect glucagon secretion in mice, but their effects on the secretion of other islet hormones have not been established in rodents. In the present study, we have examined the influence of the C-terminal octapeptide of CCK, CCK-8, and GLP-1 on the secretion of pancreatic polypeptide (PP) in the mouse by the use of a radioimmunoassay for rodent PP. Mice were injected intravenously with CCK-8 (doses in the range of 0.053–5.3 nmol/kg) or with GLP-1 (doses in the range of 1–32 nmol/kg) and blood was sampled at 2, 6 or 10 min after the injection. Controls were injected with saline. It was found that CCK-8 at 5.3 nmol/kg increases plasma levels of both PP and insulin when the sample was taken at 2 min, but not at 6 or 10 min, after injection. These effects were blocked by the selective CCK A-receptor antagonist, L-364,718 (2.4 μmol/kg). GPL-1 increased plasma insulin levels at 32 nmol/kg at 2 and 6 min after the injection, but plasma PP levels were unaltered. In conclusion, this study, using a newly developed radioimmunoassay for PP in rodents, shows that CCK-8 but not GPL-1 stimulates PP secretion in mice at does levels where both peptides stimulate insulin secretion. Furthermore, PP secretion in response to CCK-8 showed a similarity with that of insulin in terms of dose- and time-response characteristics as well as sensitivity to CCK A-receptor antagonism.

Cephalic phase of pancreatic polypeptide release: a valid test of autonomic neuropathy in diabetics?

We investigated pancreatic polypeptide (PP) release by chew and spit sham feeding as a test of autonomic function in 33 patients with diabetes mellitus (DM) and 24 age-matched healthy controls. Plasma samples were taken at nine 5-min time intervals, and PP plasma levels were determined by radioimmunoassay. Autonomic neuropathy (AN) was diagnosed and staged according to four standardized tests of cardiovascular autonomic function. The integrated PP response during sham feeding was decreased in DM patients (1067 ± 397 vs. 2670 ± 394 pg/ml/30 min; P < 0.05). The maximum increase of PP plasma levels was significantly different between the DM subgroups with AN (36 ± 19 pg/ml; n = 13) and without AN (132 ± 36 pg/ml; n = 20) but varied widely in healthy controls (219 ± 29 pg/ml; range 20–460 pg/ml). A cutoff of maximum PP increase < 20 pg/ml (specificity 100%) resulted in only 46% sensitivity, while a cutoff < 160 pg/ml (sensitivity 100%) yielded 38% specificity for diagnosis of AN. The diagnostic value of the PP test for identifying individual patients against the variable reference range is therefore limited. Maximum PP increase < 20 pg/ml indicates AN, while maximum PP increase > 160 pg/ml excludes AN in diabetic patients.

Effect of antrectomy and truncal vagotomy on erythromycin induced pancreatic polypeptide secretion

Erythromycin, a motilin agonist, enhances gastrointestinal motility but also stimulates endogenous pancreatic polypeptide (PP) secretion. We investigated whether the effect of erythromycin on PP release is dependent on (1) prokinetic activity of erythromycin generated from the antrum and (2) the long vagus nerve since erythromycin acts via cholinergic neurons. Erythromycin induced PP secretion was determined in 14 patients with antrectomy (6 patients with Billroth I type anastomosis, 8 patients with Billroth II type anastomosis), in 6 patients with truncal vagotomy and pyloroplasty but without gastric resection and in 8 healthy controls. Plasma PP levels in response to erythromycin (3 mg/kg i.v.) were determined at regular intervals for 180 min. Erythromycin induced a significant increase in plasma PP in the control subjects from 22 ± 4 pmol/l (basal) to 49 ± 4 pmol/l at 10 min. In the patients with truncal vagotomy plasma PP secretion after erythromycin was significantly ( P < 0.05) increased (peak increment vs. basal: 98 ± 10 pmol/l vs. 27 ± 2 pmol/l) and prolonged compared to controls. In the patients with antrectomy no significant increases in plasma PP over basal were observed after erythromycin infusion. It is concluded that erythromycin stimulates PP secretion in healthy controls. The PP response to erythromycin is exaggerated after truncal vagotomy but absent after antrectomy indicating that the antrum is essential for erythromycin induced PP secretion.

Increased Plasma Levels of Pancreatic Polypeptide and Decreased Plasma Levels of Motilin in Encopretic Children

Objective. Abnormalities of hormones affecting gastrointestinal motility have been found in "functional" disorders of the gastrointestinal system in adults. One such disorder of childhood, encopresis, is frequently associated with constipation, the treatment of which often eliminates the soiling. We hypothesized that hormones affecting gastrointestinal motility were different between encopretic patients and matched controls. Methods. Ten encopretic patients were matched by age, race, and sex with controls who had no history of encopresis or constipation. After an overnight fast, each child consumed a meal of Ensure, the amount of which was based on body weight. Plasma levels of gastrin, pancreatic polypeptide, cholecystokinin, motilin, thyroxine, estrogen, and insulin were measured 20 and 5 minutes before the meal, and 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180 minutes after the meal. Results. Postprandial levels of pancreatic polypeptide remained consistently higher and peaked earlier (P &amp;lt; .05) for encopretic patients. The motilin response was lower (P &amp;lt; .03) for encopretic children than for controls. Conclusions. We conclude that pancreatic polypeptide and motilin responses to a meal are different in encopretic children than in children in the control group. These gastrointestinal hormone findings may in part explain and/or be the result of the severe constipation that frequently underlies the fecal soiling found in these patients. These findings also suggest the motility of the stomach and small intestine may be abnormal in encopresis.

Decreased plasma levels of cholecystokinin in healthy males after chronic ingestion of a heat-treated soya product.

Administration of raw soya containing a trypsin inhibitor stimulated excessive release of cholecystokinin (CCK) which led to pancreatic hypertrophy, hyperplasia and cancer in the rats (Booth et al. (1964) Proc. Soc. Exp. Biol. Med., 116, 1067). More postprandial CCK release in healthy humans was observed after ingestion of a single dose of raw soya than heat-treated soya (Calam et al. (1989) Br. J. Nutr., 58, 175). The effect of chronic ingestion of a heat-treated soya product on postprandial CCK release was investigated in six healthy adult males after ingestion of a 36-oz. portion of soymilk daily for 1 month and at 2-3 months after termination of soymilk ingestion. Subjects fasted for 15 h, ingested Lipomul (1.5 g/kg) and provided blood at timed intervals for CCK analysis. The results show that 1-month ingestion of soymilk decreased the magnitude of Lipomul-induced postprandial CCK release in plasma of all six subjects by 5-60% (P < 0.05) compared to those obtained at 2-3 months after the withdrawal from soymilk ingestion. Plasma pancreatic polypeptide (PP) levels were similarly decreased in five of the six subjects by 19-67% (P = 0.03) in line with the regulation of PP by CCK. Thus, prolonged exposure of humans to a heat-treated soya inhibited slightly meal-induced CCK release in contrast to that found in rats after raw soya diets.

Effects of cisapride on gallbladder emptying and pancreatic polypeptide and cholecystokinin release in humans

We investigated the effects of cisapride on gallbladder motility and on the release of pancreatic polypeptide and cholecystokinin in the fasting and postprandial states. Cisapride (7.5 mg) and/or a test meal was administered intraduodenally to seven healthy volunteers with or without atropine pretreatment (0.5 mg, i.m.). In the fasting state, cisapride increased gallbladder volume to 154% of the basal level, and significantly elevated plasma pancreatic polypeptide levels. The effects of cisapride were inhibited by atropine. In the postprandial state, integrated pancreatic polypeptide and cholecystokinin responses were increased by cisapride to 180% and 192%, respectively, of control values. Atropine inhibited the integrated gallbladder and pancreatic polypeptide response to about 60% of the control value, but did not affect the cholecystokinin response. These observations suggest that: (1) fasting gallbladder tone is influenced by cholinergic inhibitory mechanisms, (2) acetylcholine (ACh) is the final mediator for about 40% of the postprandial gallbladder emptying and pancreatic polypeptide response, and (3) coordination between the ACh-independent cholecystokinin response and ACh-dependent pancreatic polypeptide response may be important in the regulation of postprandial gallbladder emptying.

Pancreatic polypeptide enhances plasma glucocorticoid concentration in rats: Possible role in hypoglycemic stress

The acute bolus intraperitoneal (i.p.) administration of pancreatic polypeptide (PP) dose-dependently enhanced the plasma concentration of corticosterone (PBC) in hypophysectomized/ACTH replaced rats, but not that of aldosterone. Minimal and maximal effective doses were 10(-12) and 10(-10) mol/rat, respectively, and maximal PBC increase occurred between 60 and 120 min after PP injection. Insulin (1 U/kg, i.p.) evoked a net decrease in the blood glucose concentration, and marked rises in the plasma levels of PP and PBC, that attained their maximum at 60 and 120 min, respectively. The effects of insulin were annulled by the simultaneous injection of 0.5 mg/kg atropine. The effects of 1 U/kg insulin and 10(-10) mol/rat PP on PBC were not additive; atropine did not affect PBC response to PP or PP plus insulin, though annulling that to insulin alone. Taken together these findings suggest that PP plays a physiologic role in the rat as modulator of the adrenal response to the insulin-induced hypoglycemic stress.

Relationship between postprandial release of CCK and PP in health and in chronic pancreatitis

The aim of this study was to investigate the relationship between postprandial release of cholecystokinin (CCK) and pancreatic polypeptide (PP) in healthy subjects and patients with chronic pancreatitis (CP). 14 patients with CP and 14 age-matched healthy subjects were studied. Diagnosis of CP was confirmed by standardized imaging modalities (ERCP and CT). Exocrine pancreatic function was assessed in all 28 subjects using the pancreolauryl serum test (PLT). An oral test meal was administered to stimulate endogenous hormone release. Plasma samples were taken before and at several time points after the test meal. CCK and PP plasma levels were measured by specific radioimmunoassays. Basal CCK and PP plasma levels were not different between patients with CP and controls, and were not correlated in either group. However, a direct linear correlation between integrated postprandial release of CCK and PP was found in healthy subjects ( r = 0.74, P<0.005). This postprandial coupling was not evident in patients with CP ( r = 0.16; n.s.). Peak fluorescein serum concentration in patients with CP and steatorrhea (SCP) ( n = 6) was <2.5 μg/ml, and CCK and PP responses to the meal were significantly impaired ( CCK response = 61 ± 14 pmol/l/120 min in SCP vs. 110 ± 14 in controls, P<0.05; PP response = 3920 ± 1773 pg/ml/120 min in SCP vs. 13418 ± 3299 in controls, P<0.05). In patients with mild/moderate exocrine insufficiency, CCK and PP responses varied greatly and were not different from controls. Response of PP, but not CCK, was significantly correlated with the PLT result in the CP group ( r = 0.70; P<0.01). Our data point to a physiological relationship between postprandial release of CCK and PP. This link is interrupted in patients with chronic pancreatitis.