Biomedical subjects

M Rünzi

Publications and source records attributed to M Rünzi.

46 records · Page 3Linked to original sources

PubMed1993

Pancreatic duct obstruction triggers acute necrotizing pancreatitis in the opossum.

BACKGROUND: The common channel theory suggests that bile reflux, through a common biliopancreatic channel, triggers acute pancreatitis. In the present study, this controversial issue was evaluated using an experimental model of hemorrhagic necrotizing pancreatitis. METHODS: American opossums underwent ligation of the pancreatic duct alone, bile and pancreatic duct separately, or common biliopancreatic duct; the severity of pancreatitis was evaluated at selected times after ligation. RESULTS: Animals in all three experimental groups developed hemorrhagic necrotizing pancreatitis; the severity of pancreatitis was similar in each group, although only those subjected to common biliopancreatic duct ligation experienced bile reflux. CONCLUSIONS: Bile reflux into the pancreatic duct, via a common biliopancreatic channel, is not necessary for the development of pancreatitis and does not worsen the severity of pancreatitis associated with pancreatic duct obstruction in this model.

Acute Disease↗

PubMed1993

Pancreastatin--a mediator in the islet-acinar axis?

Pancreastatin was isolated from porcine pancreas in 1986 and has been shown to inhibit insulin release and exocrine pancreatic secretion in vivo. In the isolated perfused rat pancreas, we investigated its effect on the exocrine pancreas and evaluated its indirect effects mediated via the islet-acinar axis. In the presence of 16.7 mmol/L glucose, 20 pmol/L, 200 pmol/L, and 2 nmol/L pancreastatin reduced insulin release but did not affect exocrine pancreatic secretion stimulated by cholecystokinin (CCK), secretin, or bombesin. Pancreastatin also failed to affect unstimulated exocrine pancreatic secretion. In the presence of 1.7 mmol/L glucose, 200 pmol/L and 2 nmol/L pancreastatin inhibited glucagon release and potentiated CCK-stimulated exocrine pancreatic secretion. Inhibition of glucagon release and augmentation of exocrine pancreatic secretion may be independent phenomena, but they could be linked by the islet-acinar axis. Thus we speculate that a pancreastatin-induced inhibition of glucagon release may indirectly have caused augmentation of exocrine pancreatic secretion.

Animals↗

PubMed1992

Identification of somatostatin-14 and -28 in rat pancreatic juice by a new HPLC method.

Recently we could demonstrate that in rats with pancreatic hypertrophy, somatostatin is secreted in higher concentrations into the pancreatic juice than into the portal vein blood. For measurement of juice somatostatin and to characterize the molecular forms, we established a new reverse-phase HPLC method, which we describe herein. This HPLC method, using a linear gradient system consisting of 0.2% heptafluorbutyric acid in 10 mM sodium acetate and acetonitrile, showed a stable recovery rate of about 85%. Applying the pure juice to this gradient system, we detect somatostatin-14 to be the major form of immunoreactive somatostatin (IRSS) in the pancreatic juice of the rat (5% of total IRSS). The remaining 35% were found to be somatostatin-28. The role of somatostatin in pancreatic juice is not known. It raises the hypothesis that it possibly interacts with the influences intraluminal intestinal growth factors. This study supports the assumption for the existence of an insuloacinar portal system to regulate exocrine pancreatic functions by islet hormones.

Animals↗

PubMed1992

Stimulatory and inhibitory effects of galanin on exocrine and endocrine rat pancreas.

The influence of the neuropeptide galanin, present in intrapancreatic nerve endings, on the endocrine pancreas is well known. The most potent effect of galanin is inhibition of insulin release. Little is known of its effect on the exocrine pancreas. Whether galanin plays a role in the regulation of exocrine pancreatic secretion and whether this effect is mediated directly on acinar cells or indirectly via the influence on insulin secretion is not clear. In the present study, we investigated these questions using the model of the isolated and arterially perfused rat pancreas with intact exocrine and endocrine secretion. In the presence of 15.8 mM glucose in a modified Krebs-Ringer buffer and during half-maximal stimulation of enzyme secretion with 100 pmol/ml cholecystokinin octapeptide (CCK-8), a dose-response study of 0.001-100 pmol/ml porcine galanin was performed. At concentrations of 0.001 and 0.01 pmol/ml, porcine galanin significantly stimulated insulin release (p < 0.05 and < 0.01, respectively) and also significantly enhanced CCK-8-stimulated amylase secretion (p < 0.05). Doses of 0.1 and 1 pmol/ml galanin resulted in a nonsignificant inhibition of insulin release, while 10 and 100 pmol/ml strongly inhibited the endocrine response (p < 0.001). However, concentration levels of 1-100 pmol/ml galanin did not affect CCK-8-stimulated amylase secretion. Rat galanin, tested at 0.01 and 10 pmol/ml, showed no significant difference from the effects of porcine galanin at the equipotent concentrations. It is concluded that the effect of galanin on exocrine pancreas, like the effect on endocrine functions, tends to be a direct one and that it could exert a modulatory influence on the level of neuronal transmission.

Amylases↗

PubMed1992

Importance of endogenous prostaglandins for the toxicity of cyclosporin A to rat endocrine and exocrine pancreas?

Previous work has shown that cyclosporin A is toxic to the endocrine and exocrine pancreas. The aim of this study was to examine whether endogenous eicosanoids play a role in controlling cyclosporin A induced toxicity. Rats were treated for eight days with indomethacin (2 mg/kg, twice daily) in addition to cyclosporin A (5 or 10 mg/kg daily). Effects of drug treatments on exocrine (as assessed by amylase and protein secretion into the pancreatic juice) and endocrine (as assessed by the glucose dependent insulin release) pancreatic functions, and pancreatic formation of prostaglandins and thromboxane were evaluated. Treatment with cyclosporin A in the doses used did not inhibit eicosanoid formation by the pancreatic tissue ex vivo. Indomethacin caused significant inhibition of pancreatic formation of prostaglandin E2, 6k prostaglandin F1 alpha and thromboxane B2. Combined treatment with indomethacin and cyclosporin A (5 or 10 mg/kg) augmented cyclosporin A induced pancreatic toxicity with further impairment of insulin release, amylase secretion, and pancreatic juice protein content, but did not result in more pronounced inhibition of pancreatic eicosanoid formation. The increased toxicity of the combined treatment was, however, associated with raised cyclosporin A whole blood concentrations. The data suggest that the potentiation of pancreatic toxicity of cyclosporin A observed during coadministration of indomethacin is not the result of suppression of endogenous pancreatic eicosanoid biosynthesis, but more likely results from altered cyclosporin A pharmacokinetic which may be caused by an interference of indomethacin with the hepatic cytochrome P-450 dependent monooxygenase involved in cyclosporin A metabolism. The possibility that coadministration of non-steroidal antiinflammatory drugs aggravates toxic effects in cyclosporin A treated patients should be considered.

Amylases↗

PubMed1991

Glucose-dependent effects of pancreastatin on insulin and glucagon release.

Pancreastatin (PST), a peptide isolated from porcine pancreas in 1986, has been reported to inhibit insulin and to stimulate glucagon secretion. Since both of these effects have been questioned, we investigated the effect of PST (20, 200, or 2000 pM) on hormone release in the isolated perfused rat pancreas at different glucose levels (1.7, 5.5, 11.1, and 16.7 mM). At 1.7 mM glucose, 20 pM PST had no significant effect on glucagon secretion, whereas 200 pM and 2 nM PST significantly inhibited glucagon release. At a concentration of 5.5 mM glucose, insulin output was not affected by PST in any of the concentrations tested. At 11.1 mM glucose, however, 200 pM and 2 nM PST significantly inhibited insulin output. At 16.7 mM glucose, insulin secretion was significantly reduced by all concentrations of PST tested. Unstimulated exocrine pancreatic secretion was not affected by PST in any of the experimental settings. We conclude that PST inhibits glucagon and insulin secretion dose-dependently, and these effects apparently are glucose-dependent. PST does not influence basal exocrine pancreatic secretion in vitro.

Animals↗

PubMed1991

Independence of GIP-induced insulin secretion from sympathetic and parasympathetic innervation in the isolated perfused rat pancreas.

The incretin candidate GIP (gastric inhibitory polypeptide) is released from the gut by nutrients and can stimulate insulin secretion. Metabolic and hormonal factors have been shown to modulate insulin response to GIP. It is unknown, however, whether the autonomic nervous system, which itself controls insulin secretion, can modulate the insulinotropic effect of GIP. In the isolated perfused rat pancreas, we therefore investigated the influence of sympathetic and parasympathetic agonists and antagonists on the insulin response to GIP. As compared to control (6990 +/- 890 microU/10 min), the effect of either acetylcholine (29030 +/- 4600 microU/10 min), atropine (5880 +/- 1740 microU/10 min), norepinephrine (2520 +/- 750 microU/10 min), phentolamine (11380 +/- 1910 microU/10 min), isoproterenol (12740 +/- 2090 microU/10 min), propranolol (5600 +/- 880 microU/10 min), or GIP (29660 +/- 4490 microU/10 min) on insulin secretion was consistent with previous reports. The effects of the combined administration of GIP and either acetylcholine (48140 +/- 7540 microU/10 min), phentolamine (43930 +/- 4490 microU/10 min), norepinephrine (9000 +/- 1740 microU/10 min), or isoproterenol (36280 +/- 5210 microU/10 min) on insulin release were additive. Insulin response to GIP was resistant to atropine (24210 +/- 9470 microU/10 min) and propranolol (26450 +/- 4930 mu/10 min). We conclude that both GIP and the autonomic nervous system influence insulin secretion, but that they do so independently from each other.

Acetylcholine↗

PubMed1991

Cytoprotective and dose-dependent inhibitory effects of prostaglandin E1 on rat pancreas treated with ciclosporin A.

The prostaglandin E1 analogue rioprostil protects the pancreas from the noxious effect of ciclosporin A (CsA). To determine whether this cytoprotective action of rioprostil is dependent on or independent of inhibitory effects on pancreatic exocrine and endocrine secretion we studied the effect of different doses of rioprostil on pancreatic exocrine and endocrine secretions in the presence or absence of CsA. Rats received either CsA at a dose of 10 mg/kg body weight by tube feeding once in the morning, rioprostil at linearly increasing doses from 1.8 to 120 micrograms/kg body weight subcutaneously twice daily, a combination of both substances or NaCl. After 8 treatment days, the animals were operated on, and the pancreas isolated and arterially perfused. Insulin secretion was determined after stimulation with glucose, and amylase secretion after stimulation with CCK-8. Insulin and amylase secretion were significantly impaired by CsA. Rioprostil at doses of 1.8, 3.6 and 7.5 micrograms/kg body weight had no significant effect on insulin secretion in the absence of CsA but significantly improved insulin secretion in the presence of CsA. Higher doses of rioprostil significantly inhibited insulin secretion both in the presence or absence of CsA. Amylase secretion was not influenced by rioprostil at doses up to 15 micrograms/kg body weight but improved significantly amylase secretion in the presence of CsA. CsA blood and pancreatic tissue levels were not influenced by rioprostil at doses up to 120 micrograms/kb body weight. We conclude that the cytoprotective effect of the prostaglandin E1 analogue rioprostil against the noxious effect of CsA is dose dependent and is not related to its inhibitory action on endocrine and exocrine pancreatic secretion.

Amylases↗

PubMed1991

[Effect of pancreastatin on insulin secretion and the exocrine pancreas in rats].

Pancreastatin, a 49-amino-acid C-terminal amidated peptide, was isolated from porcine pancreas in 1986. It has been reported to inhibit insulin release and exocrine pancreatic secretion, but both these effects have been disputed. In the isolated perfused rat pancreas we therefore studied the effect of pancreastatin on insulin and exocrine pancreatic secretion. Neither basal exocrine pancreatic secretion, nor exocrine secretion stimulated by CCK-8, bombesin or secretin were affected by pancreastatin. 20 or 200 pM pancreastatin, however, significantly inhibited stimulated insulin release. We conclude that pancreastatin seems to be yet another inhibitory peptide, which--for unknown reasons--inhibits insulin release both in vivo and in vitro, but exocrine pancreatic secretion only in vivo.

Animals↗

PubMed1989

Effect of neural blockade on somatostatin-induced inhibition of exocrine pancreatic secretion.

In vivo somatostatin inhibits exocrine pancreatic secretion. In in vitro experiments, such as the isolated perfused pancreas, somatostatin fails to inhibit exocrine pancreatic secretion. This suggests an indirect action of somatostatin, such as modulation of neural regulation. In the anesthetized rat we tested the inhibitory capacity of somatostatin in the presence of neural blockade in vivo. Neither the drugs given intravenously--phentolamine, propranolol, atropine and naloxone--nor vagotomy were able to prevent somatostatin-induced inhibition of exocrine pancreatic secretion. We conclude that somatostatin-induced inhibition of exocrine pancreatic secretion is not dependent on intact extrinsic innervation.

Animals↗