Regulation of the exocrine pancreas in growing pigs, with special emphasis on entero-pancreatic reflexes

Sammanfattning: The regulation of the exocrine pancreas has been under thorough investigation for many decades. In rats, cholecystokinin (CCK) is considered to be the major gut hormone stimulating the pancreas to releasing the digestive enzymes. CCK acts directly via CCK-A receptors in the pancreas, or through receptors located on the vagal afferents and stimulating the secretion via the cholinergic vagal efferents. The regulation of the pancreas in pigs, as studied in this thesis, appears to be more complex, since the pancreatic acinar cells in pigs do not possess CCK-receptors and CCK given to the general circulation, in doses mimicking physiological levels, fail to stimulate exocrine secretion. However, in experiments where similar physiological doses of CCK have been given directly to the duodenal circulation, pancreatic enzyme secretion was stimulated. The major aim of this thesis was to clarify the role of CCK in the regulation of the exocrine pancreas in pigs and to determine the role and location of the CCK receptors. This was done by using directed local or general administration of CCK, in catheterised weaned pigs and CCK receptor blockers. The effect of the duodenal infusion of vegetable oils differing in their fatty acid composition, on the food-stimulated exocrine pancreatic secretion was also studied in chronically catheterised pigs. In addition, the possibility of inducing the maturation of the exocrine pancreas in suckling piglets, by enteral exposure to kidney bean lectin, was investigated. The results implied that CCK is involved in the regulation of the exocrine pancreas in pigs. Using the CCK-A receptor blocker, Tarazepide, and the CCK-B receptor blocker, YF476, it was determined that there were no functional CCK-A receptors in the pancreas or duodenum; instead the CCK-A receptors were located elsewhere and only acted at supraphysiological doses of CCK. The results suggested that the stimulating effect of CCK is probably mediated by CCK-B receptors located in the duodenum, with the effect on the exocrine pancreas being mediated via short entero-pancreatic reflexes. The major change obtained after the duodenal administration of vegetable oils, having different fatty acid profiles, was a decrease in the volume while the enzyme secretion was unaffected after infusion with olive oil, and an elevated colipase output after infusion with coconut oil. Treatment of 10-day old suckling pigs with a preparation of kidney bean lectins for three days led to a significant enhancement of the fluid secretion, the protein output, and the output of the enzymes, trypsin and amylase during CCK-stimulation in comparison to that observed in the control littermates. In addition, the basal plasma insulin levels were reduced after the lectin-treatment. The results suggested that there was an increased capacity for pancreatic enzyme secretion in the lectin-treated suckling piglets. Such increased pancreatic function might ameliorate the difficulties that may appear in modern pig production associated with abrupt weaning.