Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have suggested that the metabolism of methyl groups is an important factor in the function of the exocrine pancreas. Ethionine, an inhibitor of cellular methylation reactions, produces hemorrhagic pancreatitis when administered to mice fed a choline-deficient diet. Glycine N-methyltransferase, an enzyme which regulates the ratio of S-adenosylmethionine to S-adenosylhomocysteine, is particularly abundant in the exocrine pancreas. Since de novo synthesis of methyl groups requires the participation of folate coenzymes, we investigated the effect of folate deficiency on pancreatic exocrine function. Rats were fed an amino acid-defined folate-deficient diet or the same diet supplemented with folate ad libitum. A third group received the folate supplemented diet pair-fed to the deficient group. After 3 and 5 wk, pancreatic amylase secretion was measured in perfused duodenal segments of anesthetized animals before and after cholecystokinin injection. Pancreatic secretion was significantly reduced in the deficient group compared with the pair-fed control group after 5 wk. These results indicate that severe folate deficiency impairs pancreatic exocrine function.
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PMID:Folate deficiency inhibits pancreatic amylase secretion in rats. 752 61

Several experimental studies suggest that disturbed methylation can influence cellular differentiation in the pancreas and contribute to toxic injury in ways that enhance the pathogenesis of pancreatitis and carcinogenesis. In vitro development of fetal rat pancreas requires a basal level of methionine, but full differentiation requires a higher methionine level. Involvement of methylation in normal differentiation is supported by reports of development of hepatocyte-like cells in the pancreas of rats fed a choline-deficient diet. The administration of ethionine by feeding to mice in a choline-sufficient diet caused a lower incidence of acute hemorrhagic pancreatitis than in mice given a choline-deficient diet. Feeding or injections of ethionine in choline-sufficient diets induces low grade pancreatitis and pancreatic atrophy in rats. In the N-nitrosobis(2-oxopropyl)amine-induced model of ductal adenocarcinoma in hamsters, the latent period for induction of carcinomas has been dramatically reduced by the intermittent feeding of a choline-deficient diet combined with ethionine treatment. A recent epidemiologic study in smokers indicates that the risk of pancreatic carcinoma is inverse to serum levels of folate. These studies suggest that compromised methyl metabolism might be associated with pancreatic cancer risk in humans. Finally, it has recently been demonstrated that serum homocysteine and erythrocyte S-adenosylhomocysteine levels are elevated, and erythrocyte S-adenosylmethionine content is reduced in patients with diabetes mellitus and renal failure, likely reflecting disturbed methylation pathways. The latter may contribute to the pathogenesis of complicating lesions in diabetes. These studies suggest that disturbed methyl metabolism may contribute to the pathogenesis of several pancreatic diseases.
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PMID:Abnormal methyl metabolism in pancreatic toxicity and diabetes. 1216 95