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Sökning: onr:"swepub:oai:DiVA.org:liu-25646" > Long-term effects o...

Long-term effects of cholecystokinin on exocrine and endocrine pancreas

Gasslander, Thomas, 1952- (författare)
Linköpings universitet,Kirurgi,Hälsouniversitetet
 (creator_code:org_t)
ISBN 9178706297
Linköping : Linköpings universitet, 1991
Engelska 61 s.
Serie: Linköping University Medical Dissertations, 0345-0082 ; 337
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
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  • The gastrointestinal hormone cholecystokinin (CCK) is known to be oneof the most potent stimulators of pancreatic growth. CCK is alsosuggested to be an initiator and/or promotor of pancreatic carcinogenesis. This study was undertaken to elucidate the effects oflong-term stimulation with exogenous and endogenous CCK andexogenous secretin on exocrtne and endocrine pancreatic cell proliferation (in rats and mice) and on . endocrine (B-cell) function (inrats). Cell kinetics were studied autoradiographically by means of 3H-thymidine labeling of DNA synthesizing cells and endogenous increasein plasma CCK level was induced by surgical pancreatico-biliary diversion (PBD). The study showed that long-term stimulation with the CCK analogue cerulein (in mice) as well as endogenously induced hyperCCKemia (in rats) induced pancreatic hyperplasia. The proliferative response was as high, or even higher, in the ductal and centroacinar cell populations than in the acinar one, which traditionally is regarded as the target forCCK. The cells adapt to the continuous CCK stimulation with a decrease in proliferative activity to control level after 14-20 days. Cerulein seems to induce early changes in the centroacinar cell region with signs of transition of cells from acinar to centroacinar position. Secretin, which has the ductal cells as its main target cell, had no growth stimulating effect on any of the studied cell types. Long-term endogenous CCK stimulation does not affect the proliferation of cells in the islands of Langerhans, nor affect the insulin secretory response or the glucose elimination following intravenous glucose loading. The results of the study are of special interest as human pancreatic carcinoma is considered to be ductal and as there are suggestions of early changes in the centroacinar · region in experimental pancreatic carcinogenesis. Funhermore, the PBD model was found to be suitable for studies on longterm CCK effects, as the pancreatic growth response following PBD was exclusively caused by the increased plasma CCK level.

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