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

Abstract

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.

Abstract (Swedish)

Popular Abstract in Swedish

Bukspottkörteln (pankreas) består av en exocrin och en endocrin del. Den exocrina delen som studerats i denna avhandling innerhåller acinarceller som producerar bukspott innehållande matsmältningsenzymer. Dessa enzymer spjälkar proteiner, kolhydrater och fetter som finns i födan, till sina mindre beståndsdelar aminosyror, monosackarider och fettsyror. Efter sekretion av bukspott till tunntarmens övre del (duodenum) sker spjälningen, varefter nedbrytningsprodukterna kan absorberas av tarmslemhinnan. När födan når duodenum stimulerar den frisläppning av ett hormon, cholecystokinin (CCK), från körtelceller (I-celler) som finns i duodenums slemhinna. CCK stimulerar enzymsekretionen från exocrina pankreas genom att binda till CCK-A och CCK-B receptorer. Reglering av enzymsekretionen från pankreas hos råtta är välstuderad. Acinar cellerna med CCK-A receptorer, aktiveras till enzymfrisättning efter CCK bindning. CCK kan även utöva sin verkan indirekt genom att binda in till receptorer på nerver som når pankreas. CCK har således en hormonell och en nervös medierad verkningsmekanism som samverkar och stimulerar pankreas att frisätta enzymer.



Regleringen av pankreas hos gris är inte lika välstuderad och CCKs betydelse härvidlag är ifrågasatt, eftersom CCK receptorer saknas på acinar cellerna hos gris. Vid intravenös administrering av CCK krävs betydligt högre doser jämfört med naturligt förekommande CCK nivåer i blodet efter måltid.



I Arbete I och II studeras CCK och CCK receptorers betydelse för pankreas sekretion av enzymer samt var CCK receptorerna är belägna. I dessa studier påvisades att CCK har betydelse för sekretion av enzymer från pankreas. Sekretionen stimuleras via en entero-pankreatisk reflex efter aktivering av CCK-B receptorer belägna i duodenum.



I arbete III studeras betydelsen av fettsyrors längd och sammansättning för foderstimulerad frisättning av enzymer från pankreas. Resultaten visade att vätskevolymen var lägre hos grisar som fick olivolja direkt till duodenum. Utsöndringen av enzymet colipas var högre hos grisar som fått kokosnötolja direkt till duodenum.



I arbete IV studeras möjligheten att påskynda mognaden av och därmed enzymfrisättning från pankreas hos diande griskultingar. Detta för att övervinna de problem som uppkommer vid abrupt avvänjning. I dessa studier kunde vi påvisa en ökad enzymfrisättning efter stimulering med CCK hos grisar som matats med lectiner från kidney bönor.

• author: Evilevitch, Lena
• supervisor: [unknown] [unknown]
• opponent: Docent Ekblad, Eva, Lunds Universitet, Inst. Fysiologiska Vetenskaper, Neuroendokrin cellbiologi, LU, BMC F10, 221 84 Lund
• organization: Department of Biology
• publishing date: 2004
• type: Thesis
• publication status: published
• subject: Zoology
• keywords: kidney bean lectin, Animal physiology, Djurfysiologi, duodenum, entero-pancreatic reflex, insulin, lipas, amylas, trypsin, weaning, development, maturation, inhibition, CCK-receptors, Exocrine pancreas, CCK, pig
• pages: 96 pages
• defense location: Zoofysiologiska husets hörsal, Helgonavägen 3B, Lund
• defense date: 2004-04-30 09:15:00
• ISBN: 91-85067-10-5
• language: English
• LU publication?: yes
• additional info: Article: I.L. Evilevitch, B.R. Weström and S.G. Pierzynowski. CCK regulates pancreatic enzyme secretion via short duodenal-pancreatic reflexes in pigs. Scand. J Gastroenterol. 2003 (2): 201-206.II.L. Evilevitch, B.R. Weström and S.G. Pierzynowski. The CCK B receptor antagonist YF476 inhibits pancreatic enzyme secretion at a duodenal level in pigs. Accepted for publication in Scand J Gastroenterol. 2004. Article: III.S. Jacob, R. Zabielski, R.Mosenthin, J.L.Valverde Piedra, L.Evilevitch, M. Kuria, C.Rippe, M. Sörhede Winzell and S.G. Pierzynowski. Influence of intraduodenally infused olive and coconut oil on postprandial exocrine pancreatic secretions of growing pigs. J. Anim. Sci. 2001. 79:477-485. Article: IV.L. Evilevitch, S.G. Pierzynowski, A. Linderoth, B. Ahrén, Ch Erlanson-Albertsson, M Podgurniak and B.R. Weström Three days of enteral exposure to a red kidney bean lectin preparation enhances the pancreatic response to CCK stimulation in suckling pigs. Submitted for publication in Biol Neonate, 2004. The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Animal Physiology (Closed 2011) (011011000)
• id: d83c2117-4d5f-4aa7-a0d2-62955045e3db (old id 466924)
• date added to LUP: 2016-04-04 12:11:01
• date last changed: 2018-11-21 21:09:29