Die Wirkung von Orexin B auf die Hormonsekretion ( Insulin, Glukagon und Somatostatin ) des isoliert perfundierten Rattenpankreas

Nachdem 1998 die Orexine entdeckt wurden, sind primär zahlreiche Untersuchungen weltweit bezüglich ihrer Wirksamkeit auf das zentrale Nervensystem durchgeführt worden. Die Identifizierung der Orexinrezeptoren sowie vermehrte Hinweise auf eine mögliche auch peripher existierende Wirkung der Orexine f...

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Bibliographic Details
Main Author: El-Zayat, Bilal Farouk
Contributors: Arnold, Rudolf (Prof. Dr. med.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2003
Online Access:PDF Full Text
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Table of Contents: After the discovery of orexins in 1998, numerous investigations were made world-wide concerning their effectiveness on the central nervous system. The identification of the orexin-receptors in the digestive system as well as increased hints to a possible peripheral effect of the orexins led to the aim of this study: the peripheral influence of orexin B on the hormone secretion of the pancreas should be examined. The rat pancreas was surgically isolated and perfused after activation of the secretory function of the endocrine cells by 10 mmol glucose which was added to the perfusion-solution. Successively the influence of the different substances on the pancreas was examined by addition to the perfusion medium. Thus different orexin B concentrations as well as the effect of leptin, GLP-1 and arginine on the pancreas were examined. The samples were then examined for their content of insulin, glucagon and somatostatin by radioimmunoassay. The results showed that high concentrations of orexin B cause a stimulation of the insulin secretion of the rat-pancreas. The impact of leptin as an inhibitor of the insulin secretion could also be proven in these investigations. Leptin works as a functional antagonist of the orexin B. The studies concerning the influence of orexin B on the GLP-1 stimulated insulin secretion showed a small increase of insulin. However it seems that the used dosage could strengthen the strong effect of the GLP-1, even if only a little. The combined perfusion with orexin B and arginine showed a clear increase of the insulin secretion, so that a mutual amplification of both substances regarding the stimulation of the insulin secretion must be supposed. Regarding the secretion of glucagon, orexin B shows a clear inhibiting effect on the pancreatic function of the rat. We found that arginine which is a well-known potent stimulator of the glucagon-secretion is lightly limited in its effect by orexin B. The orienting investigations regarding the influence of the secretion of somatostatin showed no recognizable effect of orexin B to the secretory function of the endocrine pancreas. Further investigations regarding the detailed influence of orexin B in the metabolic system should follow, e.g. with higher dosages of the hormone. On the other hand investigations concerning the receptor effect would be helpful for the comprehensive understanding of its role in the metabolic system. Moreover, studies concerning the receptor density on the pancreatic cells, which identify the exact function as well as the numerical and regional distribution of the OX-2-receptors, should follow.