PubMed Health⌕ Search

Biomedical subjects

M K Müller

Publications and source records attributed to M K Müller.

At least 37 records · Page 2Linked to original sources
PubMed1993

Endogenous somatostatin possibly controls pancreatic growth: further evidence for feedback regulation.

Specific inhibitors acting upon pancreatic proteinases in the gut can cause pancreatic hypertrophy ('growth'), which is probably mediated through a feedback mechanism utilizing cholecystokinin. We have proposed the involvement of somatostatin, and here test the hypothesis that endogenous somatostatin secreted into pancreatic juice may regulate pancreatic growth. Groups of rats were given the proteinase inhibitor camostate intragastrically for either 3, 7, 14, 28, or 56 days, when they were sacrificed. In some groups the pancreata were weighed and homogenized while in other groups isolated perfused pancreatic organ preparations were performed. Somatostatin was measured in the homogenates, pancreatic juice and portal vein effluents. In camostate-fed animals, pancreatic weights increased to a maximum at 28 days, while pancreatic somatostatin content increased significantly from the third day onwards, and somatostatin secretion into pancreatic juice increased progressively until day 28. In contrast, somatostatin secretion into portal blood remained unchanged from those of untreated controls over the duration of the experiment, and its concentration was lower than in pancreatic juice. These observations provide further evidence that endogenous pancreatic somatostatin may control pancreatic growth in rats.

Animals↗
PubMed1993

Effect of cysteamine on insulin release and exocrine pancreatic secretion in vitro.

Cysteamine is known to deplete somatostatin from pancreatic D cells. In the isolated perfused rat pancreas we investigated its effects on somatostatin and insulin release as well as exocrine pancreatic secretion in the presence of 16.7 mM glucose and 180 pM CCK-8. At a concentration of 0.1 mM, cysteamine had no significant effect on pancreatic endocrine and exocrine functions. At 10 mM, however, cysteamine released somatostatin (380 +/- 70 vs 100 +/- 20 fmol/20 min), inhibited insulin output (890 +/- 120 vs 13210 +/- 3260 mu units/20 min) and reduced exocrine pancreatic secretion (volume: 12 +/- 2 vs 20 +/- 2 microliters/20 min; lipase: 31 +/- 3 vs 60 +/- 7 units/20 min). We conclude that the complex changes induced by cysteamine are consistent with a physiological role of endogenous somatostatin in the regulation of insulin release. The reduction of exocrine pancreatic secretion, however, was at least in part, if not completely, mediated via the insuloacinar axis rather than a direct effect of cysteamine-released somatostatin on pancreatic acinar cells.

Animals↗
PubMed1993

Role of somatostatin in regulation of insular-acinar axis.

Cysteamine is known to deplete somatostatin from pancreatic D cells. In the isolated perfused rat pancreas we investigated its effects on somatostatin and glucagon release as well as exocrine pancreatic secretion in the presence of 1.8 mM glucose. Cysteamine, 10 mM, released somatostatin, but had no effect on CCK-stimulated amylase secretion. Arginine-stimulated glucagon release, however, was significantly inhibited by cysteamine. Concomitantly we still observed stimulation of somatostatin secretion, but also a potentiation of CCK-stimulated amylase secretion. Our results are consistent with a role of somatostatin in the regulation of exocrine pancreatic secretion via its effect on pancreatic A and B cells.

Amylases↗
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↗
PubMed1993

[Pathophysiologic concepts and protective possibilities in experimental pancreatic lesions].

Experimental pancreatic lesions can be induced by a number of different procedures, e.g. pancreatic hyperstimulation, intraductal application of bile acids, feeding choline deficient diet, obstruction of pancreatic duct, or reducing pancreatic blood flow. The pathogenetic mechanisms leading to pancreatic lesions include basolateral enzyme secretion, acinar cell polarisation defect, intracellular activation of proteases, and the production of free radicals and other active metabolites. The importance of these individual mechanisms in the production and progression of different experimentally-induced pancreatic lesions remains speculative. These pathogenetic concepts have inspired the study of a number of substances likely to protect the pancreas and prevent the pancreatic lesions. This paper gives an overview of the pathogenetic concepts of development of and protection against experimental pancreatic lesions produced in animal models. Special mention has been made of an animal model of pancreatic lesion produced by immunosuppressives.

Animals↗
PubMed1992

[Neuroendocrine tumors of the gastrointestinal tract. Part 2: Current therapeutic concepts].

When diagnosed, the greater proportion of functioning endocrine tumors have already metastasized. As a result, the primary aim of treatment--complete surgical removal of the growth--is possible in only a small number of patients. This gives considerable importance to palliative treatment. Interferons and somatostatin are the substances in the forefront of therapeutic interest today, cytostatic chemotherapy having proved largely ineffective and associated with considerable side effects. A feature common to interferons and somatostatin is the fact that they are much more likely to achieve a subjective improvement in clinical symptoms rather than objective remission. However, this is not disadvantage, since, in view of the slow growth of these tumors, quality of life is determined by controlling endocrine activity and not by debulking tumor mass.

Carcinoid Tumor↗
PubMed1992

[Neuroendocrine tumors of the gastrointestinal tract. 1: Clinical aspects].

Endocrine cells are characterized by common biochemical properties and specific cellular markers. Endocrine tumors, too, differ from other types of tumor in a number of ways. These have to do with the classification, the occurrence of functioning or nonfunctioning forms, benign and malignant courses, solitary or multiple presentation, as well as entopic and ectopic growth forms. The incidence of the gastrointestinal functioning tumors is about 0.5-1.0 per 100,000, the nonfunctioning tumors predominating many times over. The diagnosis of functioning endocrine tumors in the early phases of the disease is based on the biochemical demonstration of substances released into the blood, and the clinical picture is determined not primarily by the size or extent of the tumor, but by the biological effects of the tumor secretions. The clinical symptomatology associated with these tumors is often much more marked than the measurable tumor manifestation.

Carcinoid Tumor↗
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↗