Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocarcinogenesis in hepatitis B virus transgenic mice was studied by means of a correlative cytomorphological and cytochemical approach at different time points in animals from 1 to 34 mo old. HBsAg-positive ground-glass hepatocytes emerged throughout the liver parenchyma in nearly all transgenic mice during the first 4 mo after birth. The panlobular expression of HBsAg persisted until foci of altered hepatocytes appeared (6 to 9 mo of age). Three different types of foci of altered hepatocytes-namely, glycogen-storage foci, mixed cell foci and glycogen-poor foci-developed. Hepatocellular adenomas and carcinomas appeared after 11 mo. Orcein staining revealed frequent transitions between ground-glass hepatocytes extensively expressing HBsAg and glycogen-storage (predominantly clear-cell) foci containing HBsAg-positive cytoplasmic components. Similar transitions between ground-glass hepatocytes and glycogenotic (clear) cells were often found in diffuse parenchymal glycogenosis at 11 or 12 mo. Remnants of HBsAg-positive material were also detected in mixed cell foci, glycogen-poor diffusely basophilic cell foci, hepatic adenoma and hepatocellular carcinoma. These findings suggest that ground-glass hepatocytes are the direct precursor of foci of altered hepatocytes and their neoplastic descendants. The extensive expression of HBsAg is gradually down-regulated during neoplastic transformation, just as the morphological the biochemical phenotypes of foci of altered hepatocytes, hepatic adenoma and hepatocellular carcinoma in transgenic mice resemble those described in chemical hepatocarcinogenesis. The predominant sequence of cellular changes leading from glycogen-storage (predominantly clear cell) foci to mixed cell foci, hepatic adenoma and hepatocellular carcinoma is characterized by a gradual decrease in the activities of glycogen synthase, phosphorylase, glucose-6-phosphatase and adenylate cyclase, whereas glucose-6-phosphate dehydrogenase and pyruvate kinase activities increase. These alterations indicate a shift from the glycogenotic state toward an increase in the pentose phosphate pathway and glycolysis.
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PMID:Hepatic preneoplasia in hepatitis B virus transgenic mice. 792 48

It has been shown that combined high local hyperinsulinism and hyperglycemia after low-number islet transplantation into the livers of streptozotocin-diabetic rats lead to the development of hepatocellular neoplasms but a substantial cocarcinogenic effect of genotoxic streptozotocin could not be ruled out completely. Thus, we herein investigated this model in BB/Pfd rats (n = 805; nine experimental groups), which develop spontaneous autoimmune diabetes similar to human type 1 diabetes. After low-number islet transplantation (n = 450), the liver acini downstream of the islets show insulin-induced alterations: massive glycogen and/or fat accumulation, translocation of the insulin receptor, decrease in glucose-6-phosphatase activity, increase in expression of insulin-like growth factor (IGF)-I, IGF-II/mannose-6-phosphate receptor, insulin receptor substrate-1, Raf-1, and Mek-1, corresponding to clear cell preneoplastic foci of altered hepatocytes known from chemical hepatocarcinogenesis and identical to that in streptozotocin-diabetic Lewis rats. After 6 months, many altered liver acini progressed to other types of preneoplasias often accompanied by an overexpression of the glutathione-S transferase (placental form), IGF-I receptor, and transforming growth factor (TGF)-alpha. After 12 to 15 and 15 to 18 months, 52% and 100% of the animals showed one or multiple hepatocellular adenomas or hepatocellular carcinomas (HCCs), respectively. Conclusively, this study identifies combined hyperinsulinism and hyperglycemia as a carcinogenic mechanism for the development of HCCs in diabetic rats. Hepatocarcinogenesis is independent from additional genotoxic compounds (i.e., streptozotocin), but is primarily triggered by increased intracellular insulin signaling via pathways associated with cell growth and proliferation, such as the Ras-Raf-mitogen-activated protein kinase pathway and the IGF system, and secondarily involves other growth factors, such as TGF-alpha.
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PMID:Hepatocellular neoplasms induced by low-number pancreatic islet transplants in autoimmune diabetic BB/Pfd rats. 1645 45