Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ultrasonic monitoring of the pancreas following secretin stimulation has shown to cause a marked dilatation of Wirsung duct; whether this phenomenon is due to the stimulation of pancreatic secretion and/or to the effect of secretin on the sphincter of Oddi (SO) motility is unknown. In the present study pancreatic scan after secretin was performed in 11 patients with nonpancreatic diseases after premedication with glucagon (inhibition of both pancreatic secretion and SO motility) or tyropramide (inhibition of SO motor function) and in patients with different degrees of pancreatic insufficiency. Serum immunoreactive trypsinogen (IRT) levels were measured in all the subjects during the test. Premedication with glucagon completely abolished both Wirsung enlargement and serum IRT increase, while tyropramide significantly reduced, but did not abolish, the response to secretin. These results suggest that both stimulation of pancreatic secretion and the increase of SO pressure are prerequisites for a full-blown occurrence of the secretin-induced modifications of Wirsung. Within chronic pancreatitis patients, the response to secretin was exaggerated in those with a still preserved pancreatic function and it was lacking in those with severe pancreatic insufficiency.
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PMID:Ultrasonic monitoring of Wirsung duct following secretin in controls and in chronic pancreatitis patients. 330 64

The endocrine islet-cell hormones insulin and glucagon are secreted at high concentrations into an intrapancreatic portal circulation and have been reported to affect the secretion of digestive enzyme by the exocrine pancreas. In the present experiments, insulin and glucagon were injected into the celiac artery of anesthetized rats to evaluate their effects on the secretion of amylase and trypsinogen by the pancreas. Neither hormone when given alone significantly changed the output of either enzyme. However, when given with the pancreatic secretagogue cholecystokinin, each altered the effect of injection of cholecystokinin. In a dose-dependent fashion insulin increased trypsinogen output without affecting amylase output, whereas glucagon inhibited amylase output and left trypsinogen output unchanged. Thus, both hormones produced a more trypsinogen-dominant pancreatic juice than that observed with cholecystokinin alone, although in different ways. These findings suggest that the endocrine hormones insulin and glucagon may regulate secretion of digestive enzymes by the pancreas by modulating the response to stimuli of overall protein secretion such as cholecystokinin.
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PMID:Regulation of digestion. II. Effects of insulin and glucagon on pancreatic secretion. 637 8

Pancreatic trophism and pancreatic enzyme composition, and plasma levels of cholecystokinin, insulin, glucagon, and glucose in liver cirrhosis induced by chronic thioacetamide administration (0.02% in the drinking water for 12 mo) were studied in rats. Advanced liver cirrhosis was evident in all thioacetamide-treated rats. The weight of the pancreas and its contents of DNA, protein, trypsinogen, chymotrypsinogen, proelastase, secretory trypsin inhibitor, and amylase were significantly increased as compared to the controls. The pancreatic secretory enzyme content changes showed a nonparallelism, characteristic of a cholecystokinin effect. Light and electron microscopy revealed a normal pancreatic architecture. Bioassayed plasma cholecystokinin levels in both fed and 24-h-fasted cirrhotic rats were significantly higher than in the corresponding controls. The plasma glucose, insulin, and glucagon levels demonstrated hypoglycemic tendencies with a glucagon predominance. These findings indicate that advanced liver cirrhosis in the rat is accompanied by pancreatic hypertrophy and hyperplasia, which might be attributed, at least in part, to elevated circulating cholecystokinin levels.
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PMID:Pancreatic trophism in experimental liver cirrhosis. 828 79

The protective effects of glucagon on the exocrine pancreas were investigated in rats with a closed duodenal loop (CDL). A CDL in rats caused marked hyperamylasemia, pancreatic edema and pancreatic histological damage such as acinar cell vacuolization and interstitial edema. A CDL also caused redistribution of the lysosomal enzyme, cathepsin B, from the lysosomal fraction to the zymogen fraction as well as the activation of trypsinogen in pancreatic tissue. Moreover, a CDL caused a marked motality rate (40% at 48 h). However, treatment with glucagon at a dose of 1.0 mg/kg (subcutaneous injection) every 8 h (3 times) significantly inhibited these pancreatic injuries, improving the survival rate (95% at 48 h). These results indicate the important role of lysosomal enzymes in the pathogenesis of severe acute pancreatitis, and also suggest the possible usefulness of glucagon in the treatment of clinical pancreatitis.
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PMID:Glucagon ameliorates pancreatic subcellular redistribution of lysosomal enzyme in rats with acute pancreatitis of closed duodenal loop. 994 62

Fasting induces pancreatic secretory lipase, possibly through an increased utilization of fatty acids and/or ketone bodies by the acinar cells. To test this hypothesis, the effects of L-aminocarnitine (ACA), an inhibitor of mitochondrial beta-oxidation and ketone body formation, on the pancreatic enzyme composition were studied in rats. The characteristics and reversibility of the hepatic steatosis produced by ACA in fasted animals were also investigated. In fasted rats, ACA decreased the plasma levels of beta-hydroxybutyrate, glucose and insulin, but increased that of glucagon. Fasting for 3 days increased the pancreatic lipase content by 80%. Administration of ACA (3, 10 or 30 mg kg(-1) daily) for 3 days to fasted rats led to dose-related decreases in pancreatic lipase content, the fasting-induced increase was prevented even by the lowest dose. Nevertheless, ACA in the fasted rats likewise decreased the pancreatic contents of protein, amylase and trypsinogen to varying degrees, suggesting a general defect of protein synthesis. The 3-day treatment with ACA during fasting led to dose-related, marked increases in hepatic weight and triglyceride content. Light and electron microscopy revealed lipid vesicles of varying sizes in the hepatocytes; the fat deposition was predominant in the periportal zones of the hepatic lobules. By means of electron microscopy, lipid vacuoles were observed in the centroacinar cells, but not in the acinar cells of the pancreas. In rats treated with 30 mg kg(-1) of ACA daily for 3 days while they were fasted, cessation of ACA treatment and refeeding with normal chow led to normalization of the pancreatic enzyme contents within 6 days, and gradual and complete disappearance of the hepatic steatosis within 24 days. Microscopy also demonstrated complete recovery in both the liver and the pancreas. The results indicate that pancreatic secretory lipase induction during the adaptive phase of starvation is dependent on an unhindered mitochondrial beta-oxidation of fatty acids and ketogenesis. The dose-related degree of hepatic triglyceride accumulation which can be produced readily by administration of ACA during short-term starvation in the rat may serve as a new, convenient experimental model for studies of fatty liver.
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PMID:Effect of L-aminocarnitine, an inhibitor of mitochondrial fatty acid oxidation, on the exocrine pancreas and liver in fasted rats. 1060 Feb 64

The aim of the present study was to investigate the spontaneous and cholecystokinin-octapeptide (CCK-8)-promoted laboratory changes and morphological alterations in rats with arginine (Arg)-induced pancreatitis in which diabetes had been induced with streptozotocin (STZ). Male Wistar rats were used in our experiments. Pancreatitis was induced by arginine, diabetes by STZ and regeneration was promoted by CCK-8. The serum amylase, glucose and insulin levels, the pancreatic contents of protein, DNA, amylase, trypsinogen and lipase, the pancreatic weight/body- weight ratio (pw/bw) and the plasma glucagon level were examined 1, 3, 7, 14 and 28 days after pancreatitis induction. Pancreatic tissue samples were examined by light microscopy and immunostaining on paraffin-embedded sections. The insulin and glucagon-containing cells were visualized by using monoclonal antibodies. The administration of low doses of CCK-8 accelerated the processes of regeneration following Arg-induced pancreatitis, but in rats that were also diabetic, pancreatic regeneration was not observed. The administration of low doses of CCK-8 seems to reduce the pancreatic beta -cell number and function in diabetic rats. The pancreatic endocrine function was further deteriorated by simultaneous Arg-induced pancreatitis. The diabetic state appeared to shift the normal pancreatic enzyme content (decreased amylase and increased trypsinogen) in this study.
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PMID:Cholecystokinin fails to promote pancreatic regeneration in diabetic rats following the induction of experimental pancreatitis. 1171 66

To better understand the relationship between the endocrine and exocrine cell types in the Xenopus pancreas, we have cloned the Xenopus amylase cDNA and compared its expression profile with that of four other pancreatic markers: insulin, glucagon, elastase and trypsinogen. Our results demonstrate that the first pancreatic marker to be expressed is insulin, exclusively in the dorsal pancreas. These insulin-expressing cells form small groups which resemble islets, but no insulin is detected in the ventral pancreas until stage 47. In contrast, the exocrine markers, amylase, elastase and trypsinogen are first expressed only in the ventral pancreas beginning at stage 41; by stage 45 their expression extends into the dorsal pancreas. Glucagon, on the other hand, is not expressed in the pancreas until stage 45. In the endocrine cell clusters we do not find glucagon-expressing cells surrounding insulin-expressing cells, either in the tadpole or in the mature frog pancreas.
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PMID:Expression of amylase and other pancreatic genes in Xenopus. 1196 Jul 4

Within the human pancreas, exocrine and endocrine cells control secretion of digestive enzymes and production of hormones to maintain metabolic homeostasis, respectively. While the vast majority of type 1 diabetes research efforts have focused on endocrine function and autoimmunity, recent studies identified a series of unique features (e.g., reduced weight and volume, increased density of leukocytes) within the exocrine pancreas in this disease, but the mechanisms underlying these aberrancies are unknown. Therefore, we histologically assessed amylase, insulin, glucagon, lipase, and/or trypsinogen in 78 organ donor pancreata from birth through adulthood in control subjects and those at various stages of type 1 diabetes. While amylase-positive (AMY+) acinar cells were detectable in pancreata from all study groups, tissues from individuals >2 years of age contained clusters of acinar cells devoid of amylase (AMY-). A majority of these AMY- cell clusters localized proximal to islets (i.e., peri-islet). Additionally, most AMY- clusters were positive for the exocrine enzymes lipase and trypsinogen. Interestingly, type 1 diabetes pancreata displayed significant reductions in the frequency of these AMY- cell clusters. These results support a contribution of the islet-acinar axis in pancreatic development and underscore a potential role for the exocrine pancreas in the pathogenesis of type 1 diabetes.
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PMID:Temporal Analysis of Amylase Expression in Control, Autoantibody-Positive, and Type 1 Diabetes Pancreatic Tissues. 3159 39

Cells of the pancreatic islets produce several molecules including insulin (beta cells), glucagon (alpha cells), somatostatin (delta cells), pancreatic polypeptide (PP cells), ghrelin (epsilon cells), serotonin (enterochromaffin cells), gastrin (G cells) and small granules of unknown content secreted by the P/D1 cells. Secretion mechanism of some of these molecules is still poorly understood. However, Cathepsin L is shown to regulate insulin exocytosis in beta cells and activate the trypsinogen produced by the pancreatic serous acini cells into trypsin. The structure of the propeptide region of Cathepsin L is homologous to Cytotoxic T-lymphocyte antigen-2 alpha (CTLA-2 alpha) which is also shown to exhibit selective inhibitory activities against Cathepsin L. It was thought that if CTLA-2 alpha was expressed in the pancreas; then, it would be an important regulator of protease activation and insulin secretion. The purpose of this study was, therefore, to examine by immunohistochemistry the cellular localization and distribution pattern of CTLA-2 alpha in the pancreas. Results showed that strong immunoreactivity was specifically detected in the pancreatic islets (endocrine pancreas) but not in the exocrine pancreas and pancreatic stroma. Immunostaining was further performed to investigate more on localization of Cathepsin L in the pancreas. Strong immunoreactivity for Cathepsin L was detected in the pancreatic islets, serous cells and the pancreas duct system. These findings suggest that CTLA-2 alpha may be involved in the proteolytic processing and secretion of insulin through regulation of Cathepsin L and that the regulated inhibition of Cathepsin L may have therapeutic potential for type 1 diabetes.
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PMID:Immunoreactivity of cytotoxic T-lymphocyte antigen 2 alpha in mouse pancreatic islet cells. 3205 62