CCK-dependent pancreatic regulation and pancreatic functional impact on growth in young pigs.

The exocrine pancreas is mainly regulated via neuro-hormonal pathways. CCK-dependent regulatory pathways and CCK-receptor subtype involved seem to differ between mammalian species. The first aim of the thesis was to establish the physiological dose-range for CCK, to further explore the short entero-pancreatic reflex and CCK-receptor subtypes involved in the CCK-mediated regulation of the exocrine pancreas and to evaluate a possible involvement of this reflex in endocrine insulin release. This was carried out on anaesthetised pigs where CCK-33 in increasing doses was infused locally via the gastro-duodenal artery, or systemically via the jugular vein. Thus, CCK-33 in the physiological dose range, (4-32 pmol kg-1 10 min-1), mimicking post-prandial levels, increased protein- and trypsin outputs after local infusion to the antral-duodenal area, while it had no effect after the systemic infusion. Bilateral truncal vagotomy had no effect on these responses. Physiological doses of CCK-33 infused to the antral-duodenal region do not stimulate the exocrine pancreas via the CCK-2 receptor since the result cannot be reproduced with pentagastrin, another ligand for this receptor. In addition, it was shown that insulin release was not stimulated by local infusions of physiological doses of CCK-33. Taken together, the results imply that the short entero-pancreatic reflex pathway is the physiological pathway for CCK dependent regulation of the exocrine pancreas, while an effect of physiological CCK-doses on the endocrine pancreas is questionable in pigs. The second aim of the thesis was to evaluate the importance of the exocrine pancreatic function for the growth of young animals, by using pancreatic-duct ligated pigs, developing exocrine pancreatic insufficiency (EPI). An elemental diet (mimicking a pre-digested diet) was fed to young EPI-pigs, either alone or in combination with an oral pancreatin supplementation. The elemental diet was sufficient to maintain normal growth in control pigs while the EPI-pigs still showed an arrested growth. However, an oral pancreatin supplementation in combination with the elemental diet given i.v. improved growth significantly in EPI-pigs. Thus, pancreatic juice and enzyme preparations, in addition to their digestive properties, also appear to affect nutrient assimilation and anabolism in young individuals. EPI induced at 7 weeks of age caused a total growth arrest while EPI induced at 16 weeks of age had no effect on the growth compared to weight-matched control pigs. Thus, the exocrine pancreatic function is indispensable in young pigs while compensatory mechanisms develop before the age of 16 weeks, which decrease the importance of the exocrine pancreas