Biomedical subjects

R Nustede

Publications and source records attributed to R Nustede.

At least 55 records · Page 3Linked to original sources

PubMed1992

Induction of the fed pattern of human exocrine pancreatic secretion by nutrients: role of cholecystokinin and neurotensin.

The aim of the present study was to assess the role of cholecystokinin and neurotensin in converting the cyclical interdigestive pattern of pancreatic secretion into the non-cyclical fed pattern. Six healthy male volunteers were studied on 4 separate days. During each experiment a mixed liquid meal or solutions of individual nutrients were perfused intraduodenally for 180 min at 2 ml/min. The mixed meal contained 4.3 g glucose, 2.0 g fractionated soya oil, and 1.7 g casein hydrolysate per 100 ml, which delivered a caloric load of 0.9 kcal/min into the duodenum. The isocaloric and isotonic solutions of individual nutrients contained 44.5 g glucose, 17.8 g fractionated soya oil, or 44.5 g hydrolysed serum bovine albumin per liter and delivered 0.36 kcal/min into the duodenum. Duodenal aspirates and blood samples were collected at regular intervals for determination of pancreatic enzyme outputs and plasma levels of cholecystokinin and neurotensin, respectively. The mixed meal converted the cyclical interdigestive secretory pattern into the noncyclical fed pattern whereas none of the three individual nutrients abolished the interdigestive pattern. Not only the mixed meal but also lipid and protein perfusion consistently stimulated cholecystokinin release. Integrated incremental cholecystokinin release amounted to 32.3 +/- 9.9 pg/ml x 180 min with the mixed meal, 23.2 +/- 6.5 with lipid perfusion (P < 0.05 versus mixed meal) and 13.4 +/- 3.8 with protein perfusion (P < 0.05 versus mixed meal). The carbohydrate solution did not significantly release cholecystokinin. None of the duodenal perfusates raised neurotensin plasma levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

[Effect of pancreatic innervation on exocrine secretory performance of the pancreas].

In the present study we examined the influence of extrinsic pancreatic innervation on exocrine pancreatic response to secretin, caerulein, tryptophan and fat, and furthermore the amino acid- and fat-stimulated release of neurotensin and CCK in dogs. Denervation of the pancreas did not alter secretory response to secretin and caerulein, whereas transsection of the extrinsic nerves significantly diminished the protein response to tryptophan and fat. Release of CCK was not altered by pancreatic denervation. However, fat-evoked neurotensin plasma levels were significantly increased after denervation of the pancreas.

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PubMed1992

Influence of different methods of vagotomies on the secretion of cholecystokinin in dogs.

In six dogs, a selective proximal vagotomy, gastric vagotomy, and truncal vagotomy were performed successively. Basal and postprandial cholecystokinin (CCK) concentrations in the peripheral blood were measured by radioimmunoassay. After all the different types of vagotomy, especially after truncal vagotomy, an increased postprandial secretion of CCK was found compared with the healthy animal. Possible causes discussed are the cutting of vagal fibers, which might inhibit the secretion of CCK cells, and the changed gastric and pancreatic secretion.

Animals↗

PubMed1992

Endocrine response to intragastric and intravenous glucose challenge in the denervated dog pancreas.

The functional connection between the gut and the islet cells comprises nerves and gastrointestinal hormones. In this study, we quantified the incretin effect and the glucose tolerance (KG value) before and after denervation of the pancreas in dogs in order to find out whether the incretin effect is mediated by nerves. The participation of nerves was estimated by comparing metabolic tests before and after total extrinsic pancreatic denervation in 10 dogs. Fifty-nine percent of the insulin response after intragastric glucose was calculated preoperatively to be the result of incretin factors, a value similar to the 62% found in the postoperative series (with denervated pancreas). The response of GIP to intragastric glucose was not significantly different between pre- and postoperative tests. The KG values pre- and postoperative were in the same range. From our data, we conclude that extrinsic nerves of the pancreas do not seem to play an important role in mediating glucose homeostasis in dogs.

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PubMed1992

Cephalic stimulation of gastrointestinal secretory and motor responses in humans.

The present study was designed (a) to investigate the cephalic phase of gastropancreatic secretion, antroduodenal motility, and regulatory peptide release in six healthy young men and (b) to assess its regulation by the cholinergic system and endogenous cholecystokinin. Sham feeding performed for 15 minutes induced a concurrent stimulation of gastropancreatic secretion, antroduodenal motility, and pancreatic polypeptide release that lasted for 30 minutes. Reappearance of interdigestive phases III was retarded in the post-sham-fed state. Atropine abolished secretory, motor, and pancreatic polypeptide responses to sham feeding and enhanced gastrin release. The cholecystokinin receptor antagonist loxiglumide did not attenuate pancreatic enzyme response but diminished antral motor response by 72% (P less than 0.05) and release of pancreatic polypeptide by 91% (P less than 0.05); it enhanced gastrin release and abolished retardation of reappearance of phase III with sham feeding. It is concluded that (a) there is a distinct cephalic phase of gastropancreatic secretion, antroduodenal motility, and pancreatic polypeptide release in humans that is primarily under cholinergic control and that (b) endogenous cholecystokinin is involved in antral motor, gastrin, and pancreatic polypeptide responses to sham feeding.

Adult↗

PubMed1992

Effect of total extrinsic denervation and atropine on HCl-stimulated pancreatic exocrine secretion and CCK release in conscious dogs.

In 10 dogs with pancreatic fistulas, we studied the effect of extrinsic pancreatic innervation and atropine on protein and bicarbonate secretion and cholecystokinin (CCK) release after intraduodenal perfusion with HCl. Before and after extrinsic denervation of the pancreas, the dogs were given 0.05 M HCl in increasing doses (1.5-48 mmol/h). Tests were repeated with atropine. Increasing doses of HCl resulted in a dose-dependent release of protein and bicarbonate output in both the intact and the denervated pancreas. However, pancreatic denervation significantly decreased pancreatic secretion in response to low loads but not to high loads of HCl. HCl-stimulated CCK release was not altered by pancreatic denervation. In the intact pancreas, atropine significantly reduced bicarbonate and protein response to low loads but not to high doses of HCl. In the denervated gland, atropine had no further inhibitory effect on exocrine pancreatic secretion. Furthermore, atropine showed no influence on HCl-stimulated CCK release under either condition.

Animals↗

PubMed1992

[Influence of extrinsic denervation of the pancreas on food-stimulated pancreas secretion and cholecystokinin and neurotensin release in the dog].

In the present study we examined the effect of extrinsic pancreatic denervation on meal-stimulated pancreatic exocrine secretion and the release of neurotensin and CCK in dogs. Denervation of the pancreas significantly decreased protein output from preoperatively 16,661 +/- 1824 mg x 150 min to 2033 +/- 316 mg x 150 min postoperatively (p less than 0.001), and bicarbonate secretion from 297.5 +/- 36 mmol x 150 min to 104.85 +/- 16 mmol x 150 min (p less than 0.01). Release of neurotensin and CCK was not altered by interruption of the extrinsic pancreatic nerves. Our findings are consistent with the hypothesis that pancreatic secretory response to a meal is predominantly mediated by neutral extrinsic reflexes.

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PubMed1991

Total denervation of the pancreas does not alter the pancreatic polypeptide-induced inhibition of pancreatic exocrine secretion in dogs.

Pancreatic polypeptide (PP) is a potent inhibitor of pancreatic exocrine secretion in vivo. The mechanism of pancreatic inhibition by PP is unknown, but the absence of PP receptors on pancreatic exocrine cells makes a direct effect of this hormone on the gland unlikely. In this study, we investigated the hypothesis that PP exerts its inhibitory effect via extrinsic neural pathways. Ten dogs with gastric and pancreatic fistulas were given an intravenous infusion of 250 ng/kg-1 h-1 secretin and 50 ng/kg-1 h-1 caerulein over 3 h. One hour after starting the infusion, 400 pmol kg-1 h-1 porcine PP were administered over 1 h. Pancreatic bicarbonate and protein secretions were measured. Later, the pancreas was extrinsically denervated. PP infusion decreased bicarbonate secretion in the intact gland by 47% and in the denervated pancreas by 57%. Protein secretion was diminished by exogenous PP by 31% in the intact and by 44% in the denervated pancreas. Despite pancreatic denervation, PP still exerted a significant inhibitory effect. Atropine infusion completely blocked the inhibitory effect of PP on caerulein-stimulated pancreatic protein secretion both in the intact and denervated pancreas and of secretion-evoked bicarbonate output in the denervated gland. We conclude that the inhibitory action of the hormone is not mediated via extrinsic neural pathways of the pancreas, but PP may exert its effect via intrinsic atropine-sensitive mechanisms.

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PubMed1991

Plasma concentrations of neurotensin and CCK in patients with chronic pancreatitis with and without enzyme substitution.

The peptide hormones neurotensin (NT) and cholecystokinin (CCK) are commonly attributed with a physiological role in the stimulation of exocrine pancreatic secretion. However, on the other hand, little is known about the effect of diminished exocrine pancreatic function and of the resulting maldigestion on postprandial plasma levels of these two gastrointestinal peptides. We investigated, therefore, the effect of enzyme substitution therapy on the magnitude and time course of plasma concentrations of both hormones in patients suffering from severe chronic pancreatitis. Pancreatic insufficiency led to elevated NT-concentrations, in response to a standard meal, which could be reduced by enzyme replacement therapy. Prior to enzyme therapy, the mean integrated postprandial release of NT amounted to 2800 +/- 250 pg/ml after 60 min in patients with severe chronic pancreatitis. This amount was significantly reduced to 1250 +/- 150 pg/ml after 60 min after enzyme therapy, compared to 810 +/- 90 pg/ml after 60 min in healthy volunteers after the standard meal. The integrated postprandial CCK level in patients investigated was significantly lower (35 +/- 4.8 pmol/L after 60 min) without any substitution therapy, compared to the integrated peptide amount in healthy volunteers (145 +/- 13.5 pmol/L after 60 min). Enzyme therapy in patients suffering from chronic pancreatitis led to an increased postprandial CCK-level (80 +/- 9.6 pmol/L after 60 min). Elevated CCK-plasma concentrations have not been demonstrated in these patients with pancreatic insufficiency. We therefore suggest that CCK might not play a major role in feedback regulation in patients with chronic pancreatitis. However, in light of elevated NT plasma concentrations in patients with chronic pancreatitis, NT-mediated influence on the pancreas deserves further study.

Amylases↗

PubMed1991

Cholecystokinin receptor antagonist loxiglumide modulates plasma levels of gastro-entero-pancreatic hormones in man. Feedback control of cholecystokinin and gastrin secretion.

The effect of the potent specific cholecystokinin (CCK) receptor antagonist loxiglumide on meal-stimulated plasma concentrations of CCK, gastrin, pancreatic polypeptide (PP), neurotensin, glucose-dependent insulinotropic polypeptide (GIP), insulin and C peptide was investigated in a placebo-controlled study in 10 healthy male volunteers. Intravenous infusion of loxiglumide (10 mg kg-1 h-1) significantly augmented integrated incremental IR-CCK levels 7.3-fold after stimulation by a standard breakfast (504 +/- 54 vs 3.665 +/- 365 pmol-1 135 min-1, P less than 0.001), as measured by a specific CCK radioimmunoassay. Basal IR-CCK concentrations were not affected by administration of loxiglumide. Oral treatment with bile acids (2 g ursodeoxycholic acid plus 2 g chenodeoxycholic acid) together with the meal abolished this augmentation, whereas high-dose substitution with pancreatic enzymes (4.2 g pancreatin) reduced elevated IR-CCK levels by only 38%. CCK-like bioactivity, determined by a bioassay using rat pancreatic acini, was not detectable in all samples that contained loxiglumide at plasma concentrations of 100-250 micrograms ml-1. Plasma gastrin concentrations in response to the breakfast were elevated 3.2-fold during loxiglumide infusion and not influenced by substitution with bile acids or pancreatic enzymes. Meal-stimulated integrated incremental plasma PP concentrations were significantly suppressed (55-65% inhibition, P less than 0.01) by loxiglumide. Infusion of the CCK receptor antagonist only slightly increased postprandial peak plasma glucose, insulin and C-peptide levels, whereas GIP and neurotensin levels were not significantly influenced. These findings suggest: (i) CCK secretion is under feedback control by intraduodenal bile acids and to a lesser extent by pancreatic enzymes; (ii) simultaneous extraction of CCK and loxiglumide results in circulating plasma CCK-like bioactivity of zero; (iii) gastrin secretion is feedback controlled via an indirect mechanism probably involving CCK-induced somatostatin secretion; (iv) release of PP is under inhibitory control of CCK; (v) CCK does not play a major role as insulinotropic hormone in the entero-insular axis in humans.

Adult↗

PubMed1991

Role of CCK in regulation of pancreaticobiliary functions and GI motility in humans: effects of loxiglumide.

To evaluate the physiological role of cholecystokinin (CCK) in humans, we studied the influence of the specific CCK receptor antagonist loxiglumide (CR 1505) on gallbladder contraction, pancreatic enzyme output, plasma CCK concentrations, mouth-to-cecum transit time (MCTT), stool weight, and fecal fat excretion. Infusion of CCK-8, producing CCK plasma levels of 10-12 pmol/l, decreased gallbladder volume to 21% of the initial volume (P less than 0.01) and increased bilirubin output 8- to 10-fold and pancreatic enzyme secretion 2- to 4-fold. Infusion of loxiglumide (10 mg.kg-1.h-1 iv) abolished CCK-8-stimulated enzyme and bilirubin output. Basal gallbladder volume increased 68% during loxiglumide infusion (P less than 0.001) and 137% (P less than 0.001) after 7 days of oral loxiglumide treatment (3 x 1.6 g/day). Gallbladder contraction and bilirubin output in response to the intraduodenal instillation of a liquid meal (382 kcal) was completely inhibited by loxiglumide; gallbladder volume even increased 45% postprandially during loxiglumide infusion (P less than 0.02) and 145% after long-term loxiglumide treatment (P less than 0.001). Meal-stimulated pancreatic enzyme output was diminished 46-53% after acute and 25-29% after chronic administration of loxiglumide. Meal-stimulated integrated plasma CCK-immunoreactive (CCK-ir) concentrations, determined by RIA, were 3.2-fold higher during loxiglumide infusion (P less than 0.02); plateau CCK levels were markedly elevated (10.1 +/- 1.4 vs. 3.7 +/- 0.5 pM). Plasma CCK-like bioactivity, measured by a sensitive bioassay, was identical to CCK-ir levels in the absence of loxiglumide; in the presence of loxiglumide, no circulating CCK-like bioactivity was detectable, indicating complete inhibition of plasma CCK. MCTT was augmented 24% (P less than 0.05). Oral treatment with loxiglumide increased stool weight 72% (P less than 0.01) and fecal fat excretion 186% (P less than 0.001). In conclusion, 1) meal-induced gallbladder contraction and fasting tone are primarily controlled by CCK; 2) the contribution of CCK to the intestinal phase of postprandial pancreatic enzyme secretion is 40-50%; 3) GI motility and absorption are partially controlled by CCK; and 4) postprandial CCK secretion is substantially augmented by loxiglumide via an unknown mechanism.

Adult↗

PubMed1991

[Neurotensin liberation during the consumption of mineral water from Bad Mergentheimer Karlsquelle].

The contraction of the gallbladder mainly mediated by CCK after oral administration of pharmacological doses of magnesium sulfate is familiar. The same applies to the cholekinetic action of courses of sulfatic mineral water treatment. It was demonstrated in 12 patients in a controlled study that besides other known secretions of gastrointestinal hormones, there is also a significant rise of the plasma level of neurotensin when Bad Mergentheimer Karlsquelle mineral water containing sulfate (3.7 g SO4/l) is drunk on an empty stomach (300 ml, 26 degrees C). This was significantly greater (basal values 6.8 +/- 4.1 pg/ml and a maximum of 15.7 +/- 8.1 pg/ml after 40 min) than in a control group consisting of the same patients who had drunk tapwater. Whereas the involvement of the neuropeptide neurotensin in the regulation of the exocrine functions of the pancreas has been established, its effect in the regulation of gallbladder contraction is probably of rather minor significance compared to CCK.

Adult↗

PubMed1990

Measurement of tissue cholecystokinin (CCK) concentrations by bioassay and specific radioimmunoassay: characterization of the bioactivity of CCK-58 before and after tryptic cleavage.

Cholecystokinin (CCK) was measured in an extract of porcine brain by a bioassay system based on the enzyme release from isolated pancreatic acini and a specific radioimmunoassay. The tissue extract represented a crude peptide preparation of porcine brain that contained several molecular forms of CCK, most of them of high molecular weight including CCK-58. The different molecular forms of CCK in the porcine brain extract were isolated by high performance liquid chromatography (HPLC). Determination of CCK-like bioactivity and immunoreactivity after HPLC was performed in parallel by bioassay and radioimmunoassay, respectively CCK-58 was the most abundant molecular form in the porcine brain extract, followed by CCK-33, and CCK-8. Both assay systems measured similar relative concentrations of all different molecular forms of CCK. To elucidate the biological potency of CCK-58 before and after tryptic cleavage, a CCK-58-enriched fraction was prepared by HPLC. Part of this material was quantitatively cleaved by trypsin resulting in the formation of small molecular forms of CCK. Bioactivity and immunoreactivity of equal amounts of cleaved and uncleaved material (= CCK-58) were determined by bioassay and radioimmunoassay in parallel. Cleavage of CCK-58 increased CCK-like bioactivity by 260% and CCK-like immunoreactivity by 310%. These results indicate that in a rat pancreatic acini system, porcine CCK-58 exerts 25-30% bioactivity compared to smaller CCK forms. The specific CCK antiserum G-160 seems to possess 25-30% affinity to CCK-58 in comparison to trypsin-cleaved CCK-58. It can be concluded that this antiserum exhibits an affinity to different molecular forms of CCK which parallels their relative bioactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Contribution of neurotensin to the entero-pancreatic axis.

Plasma neurotensin concentrations are markedly elevated in patients with severe exocrine pancreatic insufficiency. We therefore investigated whether the exocrine pancreatic function could influence postprandial neurotensin plasma concentrations. Subsequently, we tested the hypothesis that this peptide hormone is involved in regulation of pancreatic secretion. When pancreatic juice is diverted from modified Herrera fistulas in dogs, a simultaneous application of physiological amounts of lipase reduces the elevated plasma neurotensin concentrations. On the other hand, immunoneutralisation of the circulating neurotensin inhibits pancreatic secretion. This suggests a physiological role of neurotensin in the regulation of the exocrine pancreas via an entero-pancreatic axis.

Animals↗

PubMed1990

Cholecystokinin receptor antagonist loxiglumide: influence on bilio-pancreatic secretion and gastrointestinal hormones in man.

We characterized the effect of the specific cholecystokinin (CCK) receptor antagonist loxiglumide (CR 1505) on gallbladder contraction, pancreatic enzyme output and plasma CCK concentrations determined by radioimmunoassay and bioassay. Gallbladder emptying and bilirubin output in response to the intraduodenal administration of a mixed liquid meal were completely inhibited by an intravenous infusion of loxiglumide (10 mg/kg/h). In contrast, meal-stimulated pancreatic enzyme secretion was diminished by only 30-40%. CCK concentrations in response to the test meal were 3-fold higher during infusion of loxiglumide, as determined by radioimmunoassay. In the absence of the antagonist, the bioassay measured CCK plasma levels identical to those determined by radioimmunoassay. In the presence of loxiglumide, CCK-like bioactivity was not detectable, indicating that the plasma concentrations of the CCK receptor antagonist were sufficient to abolish all circulating CCK-like bioactivity. We conclude that fasting volume and meal-induced contraction of the gallbladder are controlled by CCK. Postprandial pancreatic enzyme secretion, however, is mainly mediated by non-CCK-dependent mechanisms. Plasma CCK-like immunoreactivity is increased by loxiglumide, whereas plasma CCK-like bioactivity is zero in the presence of an CCK-receptor antagonist.

Adult↗

PubMed1989

Cholecystokinin influences pancreatic trophism following total gastrectomy in rats.

In rats, total gastrectomy (TG) has been shown to induce pancreatic hyperplasia and increased tissue concentrations of pancreatic trypsin and amylase, whereas lipase concentration was decreased. We performed total gastrectomy with the additional insertion of a duodenal tube in 17 rats. A central venous catheter was placed after 3 wk. The control groups consisted of sham-operated rats with a gastrotomy plus duodenal tube and a group of rats with only a duodenal tube. The rats received meal stimulation with a 6 mL liquid diet (3 mL oil, 2 mL amino acid solution, and 1 mL glucose) via duodenal tube upon recuperation. Blood samples were taken before as well as 5, 15, 30, and 60 minutes after the meal and analyzed for insulin, pancreatic glucagon, gastrin, and CCK by specific RIA techniques. Glucose tolerance was found to be impaired after total gastrectomy. Though insulin release was delayed compared to the controls, the integrated postprandial output was unchanged. The pancreatic glucagon release after the meal increased 83% in TG rats, compared to control rats. The baseline and postprandial gastrin values diminished 70% compared to control animals. Neither group exhibited a postprandial increase in gastrin levels. TG led to an increased postprandial CCK output of 72% compared to controls. The trophic changes of rat exocrine pancreas following total gastrectomy, therefore, could be based on an elevated postprandial release of CCK.

Animals↗

PubMed1989

The influence of the duodenal passage on postprandial neurotensin release in dogs.

All types of gastric resections induce an abnormal release of gastrointestinal hormones. The missing duodenal passage seems to be the most important factor for these disturbances. In the present study we have examined the effect of exclusion and restoration of the duodenal passage on the postprandial release of neurotensin in dogs. After feeding a standard canned dog meal, exclusion of the duodenal passage by a Billroth-II-resection caused a significant increase in postprandial neurotensin release compared to the control group (peak levels 52 +/- 5.6 to 29 +/- 6 pg/ml preoperatively, integrated output 2132 +/- 228 to 3604 +/- 213 pg/ml x 150 min. p less than 0.05). Reconstruction of the duodenal passage by the Biebl-Henly-Soupault-procedure tended the elevated neurotensin levels towards normal (peak levels 36 +/- 4.8 pg/ml, integrated output 2448 +/- 236 pg/ml x 150 min., p less than 0.05). From our data we conclude that changes in intestinal transit time are responsible for the pathological increase in neurotensin release after exclusion of the duodenal passage.

Animals↗

PubMed1989

The biological relevance of N-terminal neurotensin fragments in the regulation of exocrine pancreas secretion.

Stimulation of the exocrine pancreas is one of the biological effects attributed to the tridecapeptide neurotensin (NT). Only the C-terminal 8-13 fragment with its extremely short plasma half-life in the peripheral circulation was considered to be necessary for biological activity. The N-terminal fragments that are detectable in peripheral blood in much greater concentrations were considered to be of no importance. In order to elucidate the biological relevance of these N-terminal fragments, five dogs were infused with neurotensin at a rate (50 pmol/kg/h) that had been determined to give physiological plasma concentrations. Pancreatic secretions were collected from previously implanted modified Herrera pouches. The effects of the N-terminal fragments NT 1-8 and NT 1-11 on the exocrine pancreas secretion were tested in the same way. It was possible for the first time to demonstrate a biological effect of the N-terminal fragments found in the postprandial circulation in vivo. The plasma concentrations determined by radioimmunoassay remained within the physiological range (less than 40 pg/ml). These N-terminal neurotensin fragments may therefore participate in the hormonal regulation of the exocrine pancreas secretion.

Animals↗