Pancreatic Polypeptide Concentrations Research Articles

Timing of vagal stimulation affects postprandial lipid metabolism in humans , ,

Vagal stimulation combined with an oral fat load enhances postprandial lipemia in animals and humans. We assessed whether the observed postprandial increase in plasma lipids could be explained by changes in exogenous (chylomicron) or endogenous (VLDL) lipid metabolism and whether the timing of vagal stimulation in relation to fat intake was important. Vagal stimulation was achieved by using the modified sham feeding (MSF) technique, in which food is tasted and chewed but not swallowed. Seven healthy men consumed an oral fat load (50 g) on one occasion (control protocol). On 2 other occasions, they consumed an oral fat load combined with MSF of an appetizing meal. MSF was performed for either 1 h before or 1 h after the oral fat load. Blood was collected for 7 h and was analyzed for hormones and metabolites. The postprandial triacylglycerol response differed significantly (P < 0.001) between the 3 protocols. Both MSF studies resulted in significantly higher plasma pancreatic polypeptide concentrations compared with the control. Compared with MSF for 1 hour after fat intake, MSF for 1 h before fat intake resulted in significantly higher plasma insulin concentrations (P = 0.013), a more rapid rise in chylomicron triacylglycerol concentrations (P = 0.04), and higher VLDL triacylglycerol and apoliprotein B-100 concentrations. Vagal stimulation enhanced postprandial lipemia via effects on both chylomicron and VLDL metabolism. MSF before fat intake had more dramatic effects on postprandial lipemia than did MSF after fat intake, possibly because of increased parasympathetic activity at the time of ingestion.

Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice.

Neuropeptide Y is implicated in energy homeostasis, and contributes to obesity when hypothalamic levels remain chronically elevated. To investigate the specific role of hypothalamic Y2 receptors in this process, we used a conditional Y2 knockout model, using the Cre-lox system and adenoviral delivery of Cre-recombinase. Hypothalamus-specific Y2-deleted mice showed a significant decrease in body weight and a significant increase in food intake that was associated with increased mRNA levels for the orexigenic NPY and AgRP, as well as the anorexic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in the arcuate nucleus. These hypothalamic changes persisted until at least 34 days after Y2 deletion, yet the effect on body weight and food intake subsided within this time. Plasma concentrations of pancreatic polypeptide and corticosterone were 3- to 5-fold increased in hypothalamus-specific Y2 knockout mice. Germ-line Y2 receptor knockout also produced a significant increase in plasma levels of pancreatic polypeptide. However, these mice differed from conditional knockout mice in that they showed a sustained reduction in body weight and adiposity associated with increased NPY and AgRP but decreased POMC and CART mRNA levels in the arcuate nucleus. The transience of the observed effects on food intake and body weight in the hypothalamus-specific Y2 knockout mice, and the difference of this model from germ-line Y2 knockout mice, underline the importance of conditional models of gene deletion, because developmental, secondary, or extrahypothalamic mechanisms may mask such effects in germ-line knockouts.

Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

High-fat and high-carbohydrate diets lead to insulin resistance, gastrointestinal adaptation, and high plasma triacylglycerol concentrations. It is unclear, however, how rapidly these changes occur. We sought to determine the effects of both high-fat and high-carbohydrate evening meals on parameters of insulin resistance, hypertriglyceridemia, and gastrointestinal hormones. Twelve healthy men were studied on 4 separate occasions. On 2 occasions, the subjects received a high-fat evening meal (62% of energy from fat) and on the other 2 occasions the subjects received a low-fat evening meal (16% of energy from fat). The morning after each meal the subjects were administered either an oral-fat-tolerance test or an oral-glucose-tolerance test. Plasma samples were analyzed for glucose, insulin, fatty acids, 3-hydroxybutyrate, triacylglycerol, pancreatic polypeptide, peptide YY, and cholecystokinin. Postchallenge data were analyzed by two-way analysis of variance with interaction and fasting concentrations analyzed by repeated-measures analysis of variance. Fasting plasma concentrations of triacylglycerol were significantly elevated 12 h after each evening meal, but fatty acid and 3-hydroxybutyrate concentrations were reduced. No effects on glucose or insulin concentrations were detected. The high-fat evening meals elevated plasma cholecystokinin concentrations, reduced fasting concentrations of pancreatic polypeptide, and had no significant effect on peptide YY concentrations. The ratio of fat to carbohydrate in the evening meal produced significant effects on plasma triacylglycerol and fatty acids during both the oral-fat-tolerance and oral-glucose-tolerance tests. The present study showed that the effects of high-fat and high-carbohydrate evening meals persist at least overnight and suggests that knowledge of recent dietary history is essential to the effective design of metabolic studies.

Pancreatic polypeptide in pancreatitis

Pancreatitis is a disease with increasing incidence which can be divided into an acute and a chronic form. In both acute and chronic pancreatitis, changes in plasma concentration of pancreatic polypeptide (PP) and its regulation have been reported. In daily clinical work a serologic test for the precise diagnosis and staging of acute and chronic pancreatitis is still desirable. Therefore, many studies have investigated plasma concentrations of PP in acute and chronic pancreatitis as a diagnostic marker and as a therapeutic option to treat pancreatogenic diabetes mellitus. Although the study results are presently inconclusive and potentially contradictory, the findings are nevertheless encouraging, and indicate that PP might have a role in diagnosis, grading and estimation of the prognosis of pancreatitis. Further data and prospective controlled studies are needed to judge whether PP is of clinical value for diagnosing, staging and predicting long-term outcome in acute and chronic pancreatitis.

A meal stimulation test in the diagnosis of pancreatic endocrine tumors in multiple endocrine neoplasia type 1.

The diagnostic value of the determination of the serum pancreatic polypeptide (PP) and gastrin concentrations after a standard meal for early diagnosis of patients with multiple endocrine neoplasia type 1 (MEN 1) is controversial. The aim of this study was to clarify this issue. Thirteen patients with MEN 1, seven healthy family members, and eight healthy controls were studied. Plasma PP and serum gastrin were measured before and after the ingestion of a standardized meal. The meal caused a statistically significant (p < 0.05) increase of both PP and gastrin in all three groups studied. Concerning PP, no statistically significant difference was observed between patients and controls. In family members, the values were significantly (p < 0.05) lower than in the other two groups. On the whole, no significant differences in gastrin levels were noted between patients and controls; in family members, the values were significantly (p < 0.05) lower than in patients. All patients who had abnormally high postprandial values of PP and gastrin also had abnormally high basal values of these two peptides. The determination of serum PP and gastrin levels after a meal stimulation test in patients with MEN 1 adds no information about the presence of pancreatic endocrine tumors over that provided by basal values of the two peptides.

Extrinsic neural regulation of antroduodenal motor activity in preterm infants.

This study was designed to assess whether extrinsic neural regulation of antroduodenal motor function is present in preterm neonates. Antroduodenal motor patterns were recorded in 48 infants during fasting and after a 10 ml/kg/15 min orograstric feeding. Plasma concentrations of pancreatic polypeptide were determined before and after each feeding. Of 48 infants, 24 had adult like duodenal motor responses to feeding, and they released pancreatic polypeptide postprandially. When 18 of these 24 infants were given atropine, their heart rates increased. Feedings, however, now failed to trigger adultlike duodenal motor responses or postprandial release of pancreatic polypeptide. Those 24 infants who lacked adultlike responses failed to release pancreatic polypeptide postprandially. When a subset of 10 of these infants was given atropine, feedings failed to trigger adultlike motor responses or release of pancreatic polypeptide. We conclude that extrinsic neural regulation of duodenal motor patterns is present in only about half of preterm infants.

Bovine pancreatic secretion in the first week of life: potential involvement of intestinal CCK receptors

The aim of this study was to evaluate pancreatic juice secretion of calves in the first postnatal days, and determine a potential involvement of cholecystokinin (CCK) and intestinal CCK receptor in its regulation. Nine neonatal Friesian calves (five controls and four treated intraduodenally with FK480, a CCK-A receptor antagonist) were surgically fitted with a pancreatic duct catheter and a duodenal cannula before the first colostrum feeding. Collections of pancreatic juice and duodenal luminal pressure recordings were started early after recovery from anaesthesia and continued for 6 days. From day 2 or 3 of life, periodic fluctuations in pancreatic secretions were observed in concert with duodenal myoelectric motor complex (MMC) and variations in plasma pancreatic polypeptide (PP) concentrations. Intraduodenal administration of FK480 reduced pancreatic juice secretion while intravenous infusion of CCK had no effect. Immunocytochemistry indicated an association of mucosal CCK-A and -B receptors with neural components of the small intestine. In conclusion, periodic activity of the exocrine pancreas exists in neonatal calves soon after birth and local neural intestinal CCK-A receptors could be partly responsible for the modulation of neonatal calf pancreatic secretion.

Selective role of vagal and nonvagal innervation in initiation and coordination of gastric and small bowel patterns of interdigestive and postprandial motility

Our previous studies suggested that extrinsic innervation modulates upper gut motility but is not requisite for cyclic interdigestive and postprandial motility of the stomach. However, the specific role of vagal and nonvagal extrinsic innervation in the initiation, coordination, and pattern of gastric motility in dogs after denervation of the entire upper gastrointestinal tract remains unclear. The aim of this study was to determine the role of vagal and nonvagal extrinsic innervation in control of gastric motility patterns. Mongrel dogs were subjected first to extrinsic denervation (in situ neural isolation) of the stomach, small bowel, proximal colon, liver, and pancreas but specifically maintaining vagal innervation to the stomach alone. After fasting and fed motility patterns were measured with indwelling gastric and small bowel manometry catheters, the dogs underwent transthoracic truncal vagotomy (completion of total extrinsic denervation of stomach), and motility studies were repeated. Vagal integrity to the stomach and pancreas was confirmed by means of a modified Hollander test and serum pancreatic polypeptide concentrations after the injection of exogenous insulin, respectively. We found that a cyclic motility pattern (migrating motor complex) persisted during fasting in both the stomach and the small bowel and that the patterns of the stomach and the duodenum remained temporally coordinated before and after vagotomy. However, although a cyclic phase III activity persisted in the stomach after vagotomy, the number of contractions and the motility index during phase III were decreased, and the duration between groupings of contractions was increased. No differences were noted in the duration of postprandial inhibition after feeding meals before and after vagotomy. These observations support our hypothesis that the vagal nerves are not necessary for the initiation or temporal coordination of global fasting or postprandial gastroduodenal motility patterns but are involved in modulating the pattern of contractions during gastric phase III.

Effect of circulating peptide YY on gallbladder motility in response to feeding in humans

Background and aim. Peptide YY (PYY) is a gastrointestinal hormone which is localized in the distal small bowel, colon and rectum. It has been suggested that PYY plays an important role in the ileocolonic brake. The term ileocolonic brake refers to the phenomenon that the presence of unabsorbed nutrients in the distal gut induces slowing of gastric and pancreatic secretion and inhibits gastrointestinal motility. Because the role of PYY in the regulation of postprandial gallbladder motility is relatively unknown, the effect of PYY on gallbladder motility in response to regular meal ingestion and during the cephalic phase of meal ~mulation was studied.In addition we have determined the effect of PYY on plasma cholecystoldnin (CCK) which is the principal mediator of the intestinal phase of gallbladder contraction, and on plasma pancreatic polypeptide (PP) which is a gut peptide under strong vegat-chotinorgic control. Methods. After an overnight fast, gallbladder volumes (ultrasonograpby) and plasma concentrations of CCK, PP and PYY were measured in response to modified sham feeding and to regular feeding during intravenous infusion of a physiological dose (30 pmol/kg.h) of PYY or during intravenous infusion of saline in eight healthy volunteers (3M, 5F; 19-24 yrs). Studies were performed in a randomized crossover design on two separate days. Results. PYY significantly reduced gallbladder emptying in response to modified sham feeding from 410_+106 mL.90 min to -28_+99mL.90 min (P<O.Ol) and integrated plasma PP from 2337+_397 pmol/L-90 min to 903+_232 pmol/L.90 min (P<O.01). PYY reduced gallbladder emptying in response to regular feeding from 1646+_167 mL.90 min to 1242_+84 mL.90 min (P<O.05), tended to decrease plasma PP but enhanced plasma CCK response from 53±9 pmol/L.90 rain to 82+_17 pmoVL.90 rain (P<O.O5). Conclusion. Circulating PYY suppresses gallbladder emptying in response to feeding. PYY probably acts via vagal dependent rather than CCK dependent pathways, because CCK release was enhanced, the effect was most pronounced during the cephalic phase and PYY also reduced PP secretion.

Circadian coupling between pancreatic secretion and intestinal motility in humans.

Human interdigestive intestinal motility follows a circadian rhythm with reduced nocturnal activity, but circadian pancreatic exocrine secretion is unknown. To determine whether circadian changes in interdigestive pancreatic secretion occur and are associated with motor events, pancreatic enzyme outputs, proximal jejunal motility, and plasma pancreatic polypeptide concentrations were measured during consecutive daytime and nighttime periods (12 h each) in seven healthy volunteers using orojejunal multilumen intubation. Studies were randomly started in the morning or evening. Nocturnally, motility decreased (motor quiescence: 67 +/- 22 vs. 146 +/- 37 min; motility index: 3.59 +/- 0.33 vs. 2.78 +/- 0.40 mmHg/min; both P < 0.05) but amylase output increased (273 +/- 78 vs. 384 +/- 100 U/min; P < 0.05) and protease output remained unchanged (P > 0.05); consequently, enzyme/motility ratio increased. Amylase outputs were always lowest during phase I. Motor but not pancreatic circadian activities were associated with sleep. Pancreatic polypeptide plasma concentrations were unchanged. Consequently, intestinal motor and pancreatic exocrine functions may have different circadian rhythms, i.e., decreased motor and stable secretory activity during the night. However, the association between individual phases of interdigestive motor and secretory activity is preserved. The nocturnal increase in enzyme/motility ratio is probably not caused by increased cholinergic tone.

Effect of Helicobacter pylori infection on gastric emptying and gastrointestinal hormones in dyspeptic and healthy subjects.

There is no general agreement as regards the effect of Helicobacter pylori infection on gastric emptying in patients with functional dyspepsia. Food releases several gastrointestinal hormones, and some of these are known to contribute to the regulation of gastric emptying. The aim of this study was to investigate the influence of H. pylori on gastric emptying in dyspeptic and healthy subjects and to verify whether different hormone secretion patterns are affected by the presence of the bacterium. Twenty-seven patients affected by functional dyspepsia and 30 asymptomatic healthy subjects entered the study. H. pylori presence was assessed in controls by IgG antibodies to H. pylori and [13C] urea breath test, and that in patients by Warthin-Starry stain on gastric biopsies. After ingesting a standard solid-liquid meal, an ultrasound examination of gastric emptying was performed. Plasma concentrations of gastrin, cholecystokinin, and pancreatic polypeptide were measured in the fasting and postprandial period for 4 hours. The incidence of H. pylori infection was not higher in functional dyspepsia patients than in controls. As regards gastric emptying, no difference was detected between patients and controls with and without H. pylori infection. On the contrary, the presence of H. pylori infection determined alterations in gastrin levels, which were higher in controls than in patients. Basal CCK levels were higher in the H. pylori-negative patients than H. pylori-positive patients and controls. In conclusion, H. pylori infection seems not to cause alterations in gastric emptying, but rather alterations in gastrin levels. In contrast, the altered levels of CCK account for its involvement in the pathophysiology of H. pylori-negative dyspepsia.

Prolonged effects of modified sham feeding on energy substrate mobilization

Vagal stimulation in response to nutrients is reported to elicit an array of digestive and endocrine responses, including an alteration in postprandial lipid metabolism. The objective of this study was to assess whether neural stimulation could alter hormone and substrate metabolism during the late postprandial phase, with implications for body fat mobilization. Vagal stimulation was achieved by using the modified sham feeding (MSF) technique, in which nutrients are chewed and tasted but not swallowed. Ten healthy subjects were studied on 3 separate occasions, 4 wk apart. Five hours after a high-fat breakfast (56 g fat), the subjects were given 1 of 3 test meals allocated in random order: water, a lunch containing a modest amount of fat (38 g), or MSF (38 g fat). Blood was collected for 3 h poststimulus for hormone and metabolite analyses. Plasma insulin and pancreatic polypeptide concentrations peaked at 250% and 209% of baseline concentrations within 15 min of MSF. The plasma glucose concentration increased significantly (P = 0.038) in parallel with the changes observed in the plasma insulin concentration. The nonesterified fatty acid concentration was significantly suppressed (P: = 0.006); maximum suppression occurred at a mean time of 114 min after MSF. This fall in nonesterified fatty acid was accompanied by a fall in the plasma glucagon concentration from 122 to 85 pmol/L (P = 0.018) at a mean time of 113 min after MSF. Effects on substrate metabolism after MSF in the postprandial state differ from those usually reported in the postabsorptive state. The effects of MSF were prolonged beyond the period of the cephalic response and these may be relevant for longer-term metabolic regulation.

Effect of rectal distension on gallbladder emptying and circulating gut hormones

Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. Rectal distension enhanced maximum gallbladder emptying from 66 +/- 7% to 78 +/- 5% (P < 0.05). Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05). Integrated plasma CCK concentrations were not significantly affected. Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.

Effect of rectal distension on gallbladder emptying and circulating gut hormones

Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. Rectal distension enhanced maximum gallbladder emptying from 66 ± 7% to 78 ± 5% (P < 0·05). Distension tended to increase integrated plasma PYY from 77 ± 30 pM min to 128 ± 40 pM min in the first hour after the meal (P = 0·08) and it suppressed integrated plasma PP from 1133 ± 248 pM min to 269 ± 284 pM min in the second hour (P < 0·05). Integrated plasma CCK concentrations were not significantly affected. Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.

Cholecystokinin mediates depression of feed intake in dairy cattle fed high fat diets☆

Two experiments were conducted to investigate the effects of 1) different concentrations of dietary fat and 2) i.v. administration of a cholecystokinin receptor antagonist (MK-329) on feed intake and plasma concentrations of hormones and metabolites in dairy cattle. In Experiment 1, 4 lactating Holstein cows were used in a 4 × 4 Latin square design. Treatments were diets with 1) no fat added, 2) 30 g fat/kg feed (calcium salts of long-chain fatty acids as fat supplement), 3) 60 g fat/kg, and 4) 90 g fat/kg added. Cows were fed once daily a diet of concentrate, corn silage, alfalfa haylage, and alfalfa pellets. Dry matter intake decreased linearly with increasing concentrations of dietary fat (P < 0.0001). Overall plasma concentrations of nonesterified fatty acids (P < 0.0001), triacylglycerol (P < 0.0006), and cholecystokinin (P < 0.02), increased linearly with each level of dietary fat, but there was a linear decrease in plasma insulin (P < 0.0008). In Experiment 2, 4 nonpregnant and nonlactating Holstein heifers were used in a cross-over design in a 2 × 2 factorial arrangement of treatments. Treatments were diet (fatty acids, 27 g/kg vs 103 g/kg diet dry matter) and i.v. injections (MK-329 vs vehicle). Heifers were fed once daily a total mixed ration of corn silage, cracked corn and soybean meal with or without fat supplement. Diets were switched by period and either MK-329 (70 μg/kg body weight) or its vehicle was injected i.v. at 2 hr postfeeding. Daily dry matter intake was decreased by feeding the high fat diet (P < 0.02) but was not affected by injections. Injection of MK-329, however, increased dry matter intake by 92% in heifers fed the high fat diet during the first 2 hr postinjection compared to vehicle injection. Plasma pancreatic polypeptide concentration was increased by the high fat diet at 2 hr postfeeding (P < 0.02) but was lowered by MK-329 at 1 hr postinjection (P < 0.001). Plasma insulin was lowered by the high fat diet (P < 0.01) but was not affected by injections. The elevated plasma cholecystokinin concentration may have mediated depressed feed intake of dairy cattle fed the high fat diets.

Food-related sensory stimuli are able to promote pancreatic polypeptide elevation without evident cephalic phase insulin secretion in human obesity.

The data concerning the cephalic phase of insulin secretion (CPIS) in human obesity are controversial. We investigated the effect of a variety of sensory challenges on CPIS in 17 non-diabetic obese patients (four males, 13 females, mean age 41.1 years, mean BMI 38.7). Water, saccharin, and lemon juice were used as oral stimuli, and a complete meal was simply presented as visual and olfactory stimulations. Twelve healthy normal-weight subjects (four men, eight women, mean age 39.9, mean BMI 22.5) also underwent oral stimulation as controls, and the patients who underwent the sight and smell stimulations were also tested for pancreatic polypeptide (PP) changes in order to verify the occurrence of truly cephalic reflex during the test. Insulin levels were measured before and after each stimulation (every min for the first 5 min, and then after 10, 20, and 30 min). None of the stimuli (saccharin, lemon juice or water retained in the mouth for 2 min and were then spat out; the combined and separate sight and smell of a meal for 2 min) led to a significant increase in insulin in the obese patients (except in the case of one woman after oral stimulation). The oral stimuli led to a variable CPIS in one female and three male controls. Despite the absence of CPIS, the five obese patients undergoing all three sensory stimulations related to the meal (combined sight and smell, sight alone and smell alone) showed an early and significant increase in plasma PP concentrations within the first 3 min; this was more pronounced after the combined than after the separate exposure. Although only preliminary, these results underline the variability but substantial lack of CPIS in obese patients, thus suggesting that it can be considered a relatively rare and unrelevant event even in the presence of a true brain-mediated reflex revealed by the rapid and consistent increase in PP found in our experiments.

Cephalic Phase of Lipolysis Is Impaired in Pancreatic Insufficiency: Role of Gastric Lipase

Background: Gastric lipase contributes significantly to overall lipolysis and is regulated by interacting neuro-hormonal mechanisms. Patients with alcoholic chronic pancreatitis (ACP) have low, or even absent, activity of pancreatic lipases. In that state the secretion of gastric lipase could be essential and compensate for the pancreatic defect. However, conflicting studies have not resolved the order of magnitude of gastric lipase secretion in these patients. This could be explained by differences in regulatory mechanisms, gastric mucosal changes, and abdominal vagal tone. Methods: Nasogastric intubation with modified sham feeding and upper endoscopy including biopsies for histologic classification and Helicobacter pylori infection status were performed in eight ACP patients, and eight healthy volunteers were studied on separate occasions. Vagal nerve function was assessed by calculation of heart rate variability in ACP patients. Gastric lipase was measured in aspirates by means of enzyme-linked immunosorbent assay and an enzyme kinetic assay. Plasma concentrations of gastrin, secretin, cholecystokinin, and pancreatic polypeptide were measured throughout the study. Results: Sham feeding rapidly and significantly increased gastric lipase secretion in healthy volunteers, whereas ACP patients did not respond to sham feeding. Two of eight patients were infected with H. pylori and had mucosal changes accordingly. The lack of lipase response could not be ascribed to dysfunction of the abdominal vagus. Conclusions: The cephalic phase of gastric lipase secretion is impaired in ACP patients. Although their fundic cells continue to secrete gastric lipase, they are not subject to normal neuro-hormonal regulation.

Decreased food intake and body weight in pancreatic polypeptide-overexpressing mice

Background & Aims: Pancreatic polypeptide (PP) is a 36–amino acid hormone produced by F cells within the pancreatic islets and the exocrine pancreas. The definitive function of PP in mammalian physiology remains to be determined. This study examined the effects of chronic overexpression of PP through the development of PP transgenic mice. Methods: PP transgenic mice were created by using mouse PP complementary DNA under the control of the cytomegalovirus immediate early enhancer–chicken β-actin hybrid promoter (pCAGGS expression vector). Results: A unique line of transgenic mice was created that overexpresses PP in the pancreatic islets with low levels of expression in other tissues including the brain. Plasma PP concentrations were more than 20 times higher than those of control littermates. However, PP overproduction led to postnatal lethality in half of the pups because of markedly decreased milk intake. The remaining PP transgenic mice gained less weight with specifically reduced food intake and fat mass compared with controls, a result that was more evident in male than in female mice. The transgenic mice exhibited a reduced rate of gastric emptying of a solid meal but had normal oxygen consumption and fasting leptin levels. Immunoneutralization with anti-PP antiserum reversed the phenotypic changes of transgenic animals. Conclusions: PP could be involved in feeding and body weight regulation partly through regulation of gastric emptying. GASTROENTEROLOGY 1999;117:1427-1432

The Role of Nitric Oxide in Mediating Pancreatic Endocrine Responses to Insulin‐Induced Hypoglycaemia in the Conscious Calf

The role of nitric oxide (NO) in mediating pancreatic endocrine responses to moderate hypoglycaemia has been investigated in conscious unrestrained calves. The synthesis of endogenous NO was inhibited by the administration of N-nitro-L-arginine methyl ester (L-NAME; 100 mg kg-1 I.A.), while sodium nitroprusside was infused continuously (2-4 microg min-1 kg-1 I.V.) to mimic the tonic production of NO. This effectively abolished the rise in plasma pancreatic polypeptide (PP) concentration during moderate hypoglycaemia (0.7 nmol kg-1 insulin I.V.) and significantly reduced the response to more intense hypoglycaemia (2.0 nmol kg-1 insulin I. V.). In contrast, the glucagon response was not significantly affected in either group, although consistently higher plasma glucagon values were obtained in response to the higher dose of insulin following the administration of L-NAME. It is concluded that, in the absence of L-NAME, production of NO contributes to the PP response, but not the glucagon response to hypoglycaemia in this species under physiological conditions.

Does Intraduodenal Administration of Sucrose Polyester (Olestra) Cause Satiation in Humans?

The effect of intraduodenally perfused sucrose polyester, digestible fat or saline was compared on hunger feelings, food intake and the putative satiety hormones cholecystokinin and pancreatic polypeptide in plasma of 18 healthy volunteers in a double-blind three-period cross-over study. Sucrose polyester, digestible fat or saline was perfused directly into the duodenum. During the perfusion period a standardized meal was provided and the volunteers were asked to eat until satiation. Relative to saline perfusion, digestible fat, but not sucrose polyester, decreased prospective feeding intentions, increased a feeling of fullness and reduced hunger feelings in women (N = 9) but not in men (N = 9). Sucrose polyester tended to suppress appetite ratings less effectively than digestible fat in women. Food intake did not vary among fat, sucrose polyester and saline. Cholecystokinin and pancreatic polypeptide concentrations increased over basal value and in men as in women during perfusion of digestible fat, but not during perfusion of sucrose polyester or saline. It is concluded that at the level of the duodenum sucrose polyester suppresses hunger less effectively than digestible fat, and it does not release cholecystokinin and pancreatic polypeptide into plasma.