Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic, endocrine, and environmental factors contribute to the development of diabetes. Much information has been gathered on the homeostasis mechanisms of glucose regulation by insulin-producing pancreatic beta cells. Here we demonstrate high expression levels of gelatinase B (matrix metalloproteinase-9, MMP-9) by neutrophils in acute pancreatitis and by ductular epithelial cells in chronic pancreatitis. Because gelatinase B processes cytokines and chemokines, we investigated whether and how gelatinase B cleaves insulin. Pure human neutrophil gelatinase B was found to destroy insulin by cleavage at 10 sites. Pancreatic islet and ductular cells are relatively spared in comparison with the complete destruction of acinar cells of the exocrine pancreas in chronic pancreatitis. High expression levels of gelatinase B are maintained in the immediate proximity of insulin-secreting beta cells. Consequently, diabetes may be worsened by enzymatic degradation of insulin by gelatinase B and by the consequent enhancement of the autoimmune process. Gelatinase B is diabetogenic in acute and chronic pancreatitis by cleaving insulin.
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PMID:Gelatinase B is diabetogenic in acute and chronic pancreatitis by cleaving insulin. 1262 33

Alcoholic intake has increased in society in recent years. gamma-GTP is used as a marker of liver damage by alcohol intake, but there is no reliable marker of pancreatic fibrosis. We used animal experiments and clinical data to identify a new reliable marker of early-stage pancreatic fibrosis. Pancreatic fibrosis is induced by intra-peritoneal injection of diethyldithiocarbamate. Pancreas tissue was extracted and measured. Human pure pancreatic juice was collected by endoscopic procedures. Prolyl hydroxylase in pancreas tissue is increased in the early stage of pancreatic fibrosis. Secretion of matrix metalloproteinase from pancreatic stellate cells is increased by diethyldithiocarbamate stimulation. Pancreatic stellate cells, prolyl hydroxylase and a tissue inhibitor of metalloproteinase in human pure pancreatic juice is increased in heavy alcohol drinkers and normalized in former alcohol drinkers. Active matrix metalloproteinase 2 is detected in pure pancreatic juice of chronic pancreatitis patients. Treatment with oral camostat increases pancreatic secretory trypsin inhibitor in chronic pancreatitis patients. Experimental and clinical data indicated that matrix metalloproteinase 2 and prolyl hydroxylase are candidates as markers of early-stage pancreatic fibrosis. Clinical data showed that tissue inhibitor of metalloproteinase and pancreatic secretory trypsin inhibitor in pure pancreatic juice had potential as markers of early-stage pancreatic fibrosis.
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PMID:[Fibrosis markers in heavy alcohol drinkers]. 1788 97

Chronic pancreatitis (CP) results in impairment of exocrine as well as endocrine functions and progressive fibrosis. Previous studies, have demonstrated the presence of renin-angiotensin system receptors within different pancreatic cells. The aim of the present study was to assess the effects of renin-angiotensin system (RAS) inhibitors on serum levels of fibrosis biomarkers (matrix metalloproteinase 2 and 9 (MMP-2, MMP-9), tissue inhibitor of MMP (TIMP- 1, TIMP-2), hyaluronic acid (HA)) and fasting glucose levels in patients with alcoholic CP. Seventy seven outpatients (mean age 43 years, 62 males) with diagnosed alcoholic CP were randomly enrolled into 5 study groups depending on the RAS inhibitors administered and their doses (2.5 or 5 mg and 12.5 or 25 mg for ramipril or losartan, respectively). Venous blood was sampled monthly for a period of one year to monitor serum drug levels. MMP-2, -9, TIMP-1, TIMP-2 and HA were measured with ELISA method on the onset and at the end of the study. Only forty five patients regularly participated in follow-up visits and completed the study. The fluctuations in serum HA levels observed among patients from the remaining groups also did not reach statistical significance. Serum MMP-2 levels (P = 0.06) and MMP-2/TIMP-1 ratio (P = 0.06) showed increasing tendency in the losartan 25 mg group. High doses of ramipril and losartan statistically significantly reduced fasting glucose levels. High doses of losartan can increase the MMP-2 activity in serum of alcoholic CP patients, which potentially is likely to affect turnover of extracellular matrix proteins within the pancreas. Moreover, high doses of both RAS inhibitors decrease the fasting glucose level.
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PMID:Effects of renin-angiotensin system inhibitors on fibrosis in patients with alcoholic chronic pancreatitis. 2701 Aug 99