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

The transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) is enriched in liver and adipose tissue and controls the expression of a wide variety of genes coding for important metabolic pathways, including gluconeogenesis and lipid synthesis. To investigate the role of C/EBPbeta on glucose homeostasis, we studied mice with a targeted deletion of the gene for C/EBPbeta-/- mice. Adult C/EBPbeta-/- mice have hypoglycemia after an 18-hour fast, accompanied by lower hepatic glucose production (40% of that of wild-type mice), with no change in plasma insulin and a lower concentration of plasma free fatty acids (FFA). Glucagon infusion during a pancreatic clamp acutely stimulated hepatic glucose production by 38% in wild-type animals, with no change detected in C/EBPbeta-/- mice. Unexpectedly, both the basal and glucagon-stimulated hepatic cyclic adenosine monophosphate (cAMP) levels were lower in C/EBPbeta-/- mice, indicating an essential role for C/EBPbeta in controlling proximal signal transduction. Fasting hypoglycemia was associated with normal levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene expression, however net liver glycogenolysis was impaired in C/EBPbeta-/- mice. FFA release from isolated adipose tissue in response to epinephrine was 68% lower in C/EBPbeta-/- mice than in control animals; however, N6,O2'-dibutyryladenosine (Bt2) cAMP stimulated a twofold increase in FFA release in C/EBPbeta-/- compared with no further increase in wild-type mice. Because a deletion in the gene for C/EBPbeta reduces blood glucose and circulating FFA, it could be an important therapeutic target for the treatment of non-insulin-dependent diabetes and possibly obesity, based on designing antagonists that decrease C/EBPbeta activity.
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PMID:Hypoglycemia and impaired hepatic glucose production in mice with a deletion of the C/EBPbeta gene. 991 32

A culture system with spherical multicellular aggregates (spheroids), which are formed by the rearrangement and compaction of cell aggregates, is reported to be more useful than the traditional monolayer culture system for the culture of primary hepatocytes. By performing real-time polymerase chain reaction, we analyzed the expression of genes encoding key molecules involved in liver-specific functions, namely, cell adhesion molecules (integrin 3, cadherin 1 and connexin 32), transcription factors (hepatic nuclear factor 4alpha and CCAAT/enhancer-binding protein beta), protein and metabolic enzymes (albumin, glucose-6-phosphatase, tryptophan 2,3-dioxygenase, arginase 1 and cytochrome P450 7A1) and transporters (organic anion transporting peptide 1, multidrug resistance-associated protein 2 and bile salt export pump), in spheroids derived from rat hepatocytes. Further, we compared these expression levels with those in a hepatocyte monolayer and in liver tissue. Only the gene encoding glucose-6-phosphatase (required for sugar metabolism) was expressed at a similar level in both the monolayer culture and liver tissue for 10 days of culture; the expression of all the other genes in the monolayer culture either rapidly decreased or completely disappeared as the culture duration increased. Although the expression levels of all the genes in the spheroids tended to decrease gradually with culture time, they were consistently higher than those in the monolayer culture for at least 10 days of culture. These results suggest that hepatocyte spheroids acquire intercellular organization and largely maintain many intercellular metabolic functions. Thus, the hepatocyte spheroid culture system seems to be promising for various in vitro cell-based assays.
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PMID:Comparative analysis of gene expression in rat liver tissue and monolayer- and spheroid-cultured hepatocytes. 2005 66