sincalide and Exocrine-Pancreatic-Insufficiency

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.

Topics: Amylases; Animals; Calcium; Cholecystokinin; Diabetes Mellitus, Experimental; Exocrine Pancreatic Insufficiency; Islets of Langerhans; Magnesium; Male; Pancreas; Pancreatic Juice; Peptide Fragments; Proteins; Rats

This study investigates the effects of the islet hormones insulin (Ins), glucagon (Glu), and somatostatin (Som) with nerve stimulation (EFS) acetylcholine (ACh) and cholecytokinin-octapeptide (CCK-8) on amylase secretion and intracellular free calcium concentration [Ca(2+)](i) in the pancreas of age-matched control and diabetic rats. Either Ins, Glu or Som elicited small increases in amylase secretion from the pancreas of age-matched control animals compared to a much larger increase in amylase secretion with either EFS, ACh or CCK-8. Combining the islet hormones with either EFS, ACh or CCK-8 resulted in marked potentiation of amylase output. In the diabetic pancreas, the islet hormones had no effect on amylase secretion compared to diabetic control. Moreover, either EFS, ACh or CCK-8 evoked a much smaller increase in amylase output compared to age-matched control. In addition, the islet hormones failed to potentiate the secretory effects of either EFS, ACh or CCK-8. In fura-2 loaded acinar cells from age-matched control pancreas either Ins or Glu elicited a small increase in [Ca(2+)](i) whereas Som had no effect. Both ACh and CCK-8 evoked large increases in [Ca(2+)](i) compared to control. Combining either Ins, Glu or Som with either ACh or CCK-8 resulted in a marked elevation in [Ca(2+)](i) compared to the responses obtained with either the islet hormones, ACh or CCK-8 alone. In diabetic fura-2 loaded pancreatic acinar cells, the islet hormones had no effect on [Ca(2+)](i) compared to control and moreover, the responses were much smaller than those obtained in acinar cells from age-matched control. Both ACh and CCK-8 induced large increases in [Ca(2+)]( i) in diabetic acinar cells. However, combining the islet hormones with either ACh or CCK-8 failed to enhance [Ca(2+)](i) compared to the reponses obtained in acinar cells from age-matched control. The results suggests that [Ca(2+)](i) homeostasis is deranged during diabetes mellitus and this in turn is probably associated with reduced pancreatic amylase secretion.

Topics: Amylases; Animals; Calcium; Diabetes Mellitus, Experimental; Electric Stimulation; Exocrine Pancreatic Insufficiency; Female; Fluorescent Dyes; Fura-2; Glucagon; Insulin; Islets of Langerhans; Rats; Rats, Sprague-Dawley; Sincalide; Somatostatin

Topics: Amino Acids; Exocrine Pancreatic Insufficiency; Humans; Intestinal Absorption; Pancreatic Function Tests; Sincalide

The amino acid consumption test has been proposed as an accurate test of exocrine pancreatic function. The diagnostic accuracy of this test was determined by simultaneously measuring plasma amino acids and enzyme secretion during stimulation of the pancreas with cholecystokinin octapeptide (CCK-OP) in 60 consecutive patients suspected of having pancreatic insufficiency.. All patients underwent duodenal intubation and intravenous infusion of CCK-OP (40 ng.kg-1.h-1). Pancreatic enzyme (lipase and trypsin) outputs and plasma amino acids were measured for a period of 1 hour. Total and individual plasma amino acids were quantitated by ion-exchange chromatography. The severity of pancreatic insufficiency was graded on the basis of enzyme output during CCK-OP infusion.. There was no relationship between pancreatic enzyme output and plasma concentrations of individual or total amino acids before or during CCK-OP stimulation. Using a total amino acid decrease of 12% as the cutoff, the amino acid consumption test was 91% sensitive, but very nonspecific (21% specificity) for detection of pancreatic insufficiency.. The amino acid consumption test with CCK-OP stimulation does not discriminate between patients with normal and impaired exocrine pancreatic secretion.

Topics: Adult; Amino Acids; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Middle Aged; Pancreas; Protein Biosynthesis; Regression Analysis; Sincalide

The entero-insular hormonal axis was studied in eleven conscious Beagle dogs, loaded with glucose orally and intravenously. In five of them, exocrine pancreatic atrophy was induced by pancreatic duct occlusion with prolamine, and documented by means of the p-amino-benzoic acid test. After oral glucose, the duct-occluded dogs displayed higher blood glucose (log area 4.12 +/- 0.07 versus 3.76 +/- 0.10; p less than 0.01), less plasma insulin (log area 3.56 +/- 0.08 versus 3.99 +/- 0.08; p less than 0.01) and less cholecystokinin-like immunoreactivity (log area 2.64 +/- 0.09 versus 3.10 +/- 0.14; p less than 0.01) than controls. In controls, the peripheral venous insulin concentrations were higher after oral than after isoglycaemic intravenous glucose, and this difference was no longer demonstrable in duct-occluded dogs. In the latter, gel permeation chromatography of pool plasma after oral glucose revealed a relative decrease of cholecystokinin-like immunoreactivity species, which eluted at the positions of sulphated cholecystokinin octapeptide, cholecystokinin-33 and cholecystokinin-39, and at a position intermediate between these two. Also in the duct-occluded animals, intravenous infusion of sulphated cholecystokinin octapeptide, in addition to oral glucose, resulted in an increase in plasma insulin (log area 3.83 +/- 0.10 versus 3.64 +/- 0.06; p less than 0.01) and an improvement in oral glucose tolerance. It is concluded that in the dog 1) the absence of pancreatic acinar tissue is associated with a loss of gastrointestinal factors mediating glucose-induced insulin secretion, and 2) reduction of circulating endogenous cholecystokinin species may account at least in part for this defect.

Topics: Animals; Blood Glucose; Cholecystokinin; Chromatography, Gel; Dogs; Exocrine Pancreatic Insufficiency; Gastric Inhibitory Polypeptide; Gastrins; Glucose; Insulin; Insulin Secretion; Male; Sincalide