Pancreatic Growth and Secretion. An Experimental Study on Growth Factors in Rat and Mouse

Research output: ThesisDoctoral Thesis (compilation)

Abstract

The pancreas is a central organ in the digestion of food as well as in glucose metabolism. Its two major functions are exocrine and endocrine secretion. These are meticulously regulated processes that depend on hormonal response to gastrointestinal contents and blood glucose levels through feedback mechanisms, but also to the status of pancreas in health and diseases. The present thesis aimed at further defining regulators of pancreatic growth, maintenance and secretion. A certain focus was set on the role of epidermal growth factor (EGF).

The main regulator of pancreatic integrity and growth is cholecystokinin (CCK), which is regulated by a feedback mechanism involving pancreatic juice and bile. Inducing high plasma levels of CCK for 4 weeks, by a pancreatic-biliary diversion in rats, resulted in an increase in pancreatic weight and content of DNA, but not in an increased capacity to secrete amylase. The contents of amylase and lipase in the pancreas were decreased. Continuous infusion of EGF to mouse was found to increase pancreatic weight but not the contents of protein or amylase. A strong mitogenic stimulus on all cell types in the exocrine pancreas was found, along with increased mucosal thickness in the small intestine. No effect was seen in colon. Transforming growth factor alpha (TGF-α), which binds to the same receptor as EGF, induced hypertrophy in pancreas without affecting DNA synthesis. TGF-α gave a strong response in cell number when administrated to a human pancreatic cancer cell line, an effect blocked by an EGF receptor tyrosine kinase inhibitor, tyrphostin. EGF infused to rats was excreted in the bile and increased the joint biliary and pancreatic secretion rate in a dose dependent manner, an effect that was absent when bile was diverted. The EGF receptor has been demonstrated on the β-cells in rat. Injection of EGF decreased the blood insulin levels in rats. After glucose injection this effect was reversed. In summary, endogenous CCKemia stimulates pancreatic growth but decreases the content of pancraetic enzymes. Further, EGF probably, at least partly, exerts its effects on the pancreas and the proximal gastrointestinal tract in rats after excretion with bile. Bile and EGF seem to be important regulators of pancreatic growth and functions as well as the growth of the mucosa of the proximal gastrointestinal tract. EGF also affects blood insulin levels. EGF and TGF-α induce proliferation in a human pancreatic cell line, an effect inhibited by tyrphostins.

Details

Authors
  • Claes Hjalmarsson
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Surgery

Keywords

  • oncology, Cytology, PBD, insulin, B-cells, bile, pancreatic cancer, intestine, secretion, pancreas, proliferation, tyrphostins, CCK, epidermal growth factor, transforming growth factor alpha, cancerology, Cytologi, onkologi, cancer, Surgery, orthopaedics, traumatology, Kirurgi, ortopedi, traumatologi
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date2004 May 19
Publisher
  • Studentlitteratur AB
Print ISBNs91-628-6063-1
Publication statusPublished - 2004
Publication categoryResearch

Bibliographic note

Defence details Date: 2004-05-19 Time: 10:15 Place: Department of Surgery, Malmo University Hospital External reviewer(s) Name: Gasslander, Thomas Title: Docent Affiliation: Vrinnevisjukhuset, Norrkoping, Sweden --- Article: All experiments in this thesis, if not otherwise mentioned, were carried out at the Departments of Surgery, Faculty of Medicine, Lund and Malmö, Sweden (papers I-VI). All papers will be referred to in the text by their Roman numerals; Article: I. Ohlsson B, Jansen C, Ihse I, Axelson J. Epidermal growth factor induces cellproliferation in mouse pancreas and salivary glands. Pancreas 1997;14:94-98.II. Jansen C, Ihse I, Axelson J. Epidermal growth factor induces increased mucosal thickness of the small intestine in mouse. Eur Surg Res 1997;29:447-454. Article: III. Axelson J, Jansen C, Sternby B, Björkman A, Rehfeld JF, Ihse I. Pancreatic growth after pancreatico-biliary diversion does not increase the capacity to secrete amylase. Eur Surg Res 1999;31:187-195. Article: IV. Kullenberg B, Jansen C, Fredäng N, Ohlsson B, Axelson J. Transforming growth factor alpha (TGF-α) increases cell number in a human pancreatic cancer cell line but not in normal mouse pancreas. Int J Pancreatol 2000;28:199-205. Article: V. Jansen C, Nexø E, Ihse I, Axelson J. Intravenously administered human epidermal growth factor in the rat – Biliary excretion and influences on pancreatic secretion. Eur Surg Res 2003;35:81-85. Article: VI. Jansen C, Lundquist I, Axelson J, Ohlsson B. Does epidermal growth factor participate in the regulation of glucose and insulin levels? Manuscript. The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Surgery Research Unit (013242220), Emergency medicine/Medicine/Surgery (013240200)