Defect in pancreatic exocrine and endocrine response to
cholecystokinin in genetically diabetic otsuka long-evans tokushima
fatty (oletf) rats.
Tachibana, Issei, Toshiharu Akiyama, Kennji Kanagawa, Hisashi
Shirohara, Katsuhiko Furumi, Nobuaki Watanabe, and Makoto Otsuki.
Third Department of Internal Medicine, University of Occupational
and Environmental Health, Japan, School of Medicine, Kitakyushu 807,
Japan
APStracts 2:0225G, 1995.
Clinical as well as experimental studies in insulinopenic diabetes
mellitus have demonstrated abnormal pancreatic exocrine responses to
cholecystokinin (CCK). In the present study we examined pancreatic
exocrine and endocrine function in the recently developed genetically
diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and compared
with that in the control Long-Evans Tokushima Otsuka (LETO) rats of
the same age. Stepwise increasing doses of CCK octapeptide (CCK-8;
0.027-7.0 nmol/kg/h) evoked a characteristic biphasic dose-response
curve for pancreatic juice and protein output in the LETO rats,
whereas the OLETF rats were totally insensitive to CCK-8 stimulation.
However, the responsiveness and the sensitivity to both
carbamylcholine and secretin were similar in the two groups.
Intraduodenal infusion of casein (500 mg/h) failed to stimulate
pancreatic exocrine secretion in the OLETF rats despite a greater CCK
response than in the LETO rats (peak response; 8.43 +/- 0.97 vs 5.12
+/- 0.30 pmol/L in LETO, P<0.01). Intravenous infusion of CCK-8
(4.4 nmol/kg/20 min) caused a significant increase in serum insulin
concentrations and a concomitant decrease in glucose levels in the
LETO rats, but did not in the OLETF rats. On the other hand,
intravenous bolus injection of 1.1 mmol/kg glucose caused a greater
insulin release in the OLETF rats than in the LETO rats. In contrast,
gastric acid secretion in the OLETF rats was significantly high in
both basal and in response to intravenous infusion of CCK-8 compared
to that in the LETO rats. Four subcutaneous injections of 20 [mu]g/kg
caerulein at hourly intervals over 3 h induced acute pancreatitis in
the LETO rats, but did not elicit any significant increase in serum
amylase and lipase activities and pancreatic wet weight, nor
histologic evidence of acute pancreatitis in the OLETF rats. These
results indicate that the exocrine and endocrine pancreas of the
recently developed genetically diabetic OLETF rats are totally and
specifically insensitive to exogenous and endogenous CCK stimulation,
whereas parietal cells in these rats are sensitive to CCK
stimulation.
Received 30 May 1995; accepted in final form 20 October 1995.
APS Manuscript Number G130-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95