Mechanism of exocrine pancreatic insufficiency in streptozotocin-induced diabetes mellitus in rat: effect of cholecystokinin-octapeptide

• Published in: Molecular and cellular biochemistry Vol. 261; no. 1-2; pp. 83 - 89
• Main Authors: Patel, R, Yago, M D, Mañas, M, Victoria, E M, Shervington, A, Singh, J
• Format: Journal Article
• Language: English
• Published: Netherlands Springer Nature B.V 01-06-2004
• Subjects: Amylases - analysis; Animals; Calcium - analysis; Calcium - metabolism; Cholecystokinin - pharmacology; Diabetes; Diabetes Mellitus, Experimental - metabolism; Exocrine Pancreatic Insufficiency - chemically induced; Exocrine Pancreatic Insufficiency - etiology; Exocrine Pancreatic Insufficiency - metabolism; Islets of Langerhans - chemistry; Islets of Langerhans - drug effects; Magnesium; Magnesium - analysis; Magnesium - metabolism; Male; Pancreas; Pancreas - drug effects; Pancreatic Juice - chemistry; Pancreatic Juice - enzymology; Pancreatic Juice - metabolism; Peptide Fragments - pharmacology; Proteins - analysis; Rats; Rodents
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1023/b:mcbi.0000028741.85353.c6

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.