Mechanism of exocrine pancreatic insufficiency in streptozotocin-induced diabetes mellitus in rat: effect of cholecystokinin-octapeptide.
This study investigated the effects of cholecystokinin-octapeptide (CCK-8) on pancreatic juice flow and its contents, and on cytosolic calcium (Ca2+) and magnesium (Mg2+) levels in streptozotocin (STZ)-induced diabetic rats compared to healthy age-matched controls. Animals were rendered diabetic by a single injection of STZ (60 mg kg(-1), I.P.). Age-matched control rats obtained an equivalent volume of citrate buffer. Seven weeks later, animals were either anaesthetised (1 g kg(-1) urethane; IP) for the measurement of pancreatic juice flow or humanely killed and the pancreas isolated for the measurements of cytosolic Ca2+ and Mg2+ levels. Non-fasting blood glucose levels in control and diabetic rats were 92.40 +/- 2.42 mg dl(-1) (n = 44) and >500 mg dl(-1) (n = 27), respectively. Resting (basal) pancreatic juice flow in control and diabetic anaesthetised rats was 0.56 +/- 0.05 ul min(-1) (n = 10) and 1.28 +/- 0.16 ul min(-1) (n = 8). CCK-8 infusion resulted in a significant (p < 0.05) increase in pancreatic juice flow in control animals compared to a much larger increase in diabetic rats. In contrast, CCK-8 evoked significant (p < 0.05) increases in protein output and amylase secretion in control rats compared to much reduced responses in diabetic animals. Basal [Ca2+]i in control and diabetic fura-2-loaded acinar cells was 109.40 +/- 15.41 nM (n = 15) and 130.62 +/- 17.66 nM (n = 8), respectively. CCK-8 (10(-8)M) induced a peak response of 436.55 +/- 36.54 nM (n = 15) and 409.31 +/- 34.64 nM (n = 8) in control and diabetic cells, respectively. Basal [Mg2+]i in control and diabetic magfura-2-loaded acinar cells was 0.96 +/- 0.06 nM (n = 18) and 0.86 +/- 0.04 nM (n = 10). In the presence of CCK-8 (10(-8)) [Mg2+]i in control and diabetic cells was 0.80 +/- 0.05 nM (n = 18) and 0.60 +/- 0.02 nM (n = 10), respectively. The results indicate that diabetes-induced pancreatic insufficiency may be associated with derangements in cellular Ca2+ and Mg2+ homeostasis.
Patel
R
R
Department of Biological Sciences, University of Central Lancashire, Preston, England, UK.
Yago
M D
MD
Mañas
M
M
Victoria
E M
EM
Shervington
A
A
Singh
J
J
D000681:Amylases / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002766:Cholecystokinin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D010188:Exocrine Pancreatic Insufficiency / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects; D008274:Magnesium / Q000032:analysis / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000187:drug effects; D010189:Pancreatic Juice / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis; D051381:Rats
D010446:Peptide Fragments; D011506:Proteins; C410885:cholecystokinin 8; D002766:Cholecystokinin; D000681:Amylases; D008274:Magnesium; D002118:Calcium