Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic alcoholism is frequently associated with impaired intermediary metabolism and insulin resistance. The cellular defects leading to insulin resistance have not been clearly defined but could result from reduced insulin binding or abnormalities in any one of several postreceptor steps. The purpose of the present studies was to measure 125I-insulin binding and internalization kinetics and postreceptor response of the enzyme activity of tyrosine aminotransferase in isolated cultured rat hepatocytes. Four weeks of alcohol ingestion significantly reduced to 47% of control the 125I-insulin binding sites measured either as surface or total (after digitonin permeabilization). In contrast, 125I-epidermal growth factor binding was not significantly changed. Internalization of surface-bound 125I-insulin was decreased, but degradation was not increased, indicating that altered kinetics did not account for the change. Ethanol ingestion markedly reduced in liver cytosol some enzymes regulated by insulin and involved in glucose homeostasis. Basal activities of tyrosine aminotransferase and glucokinase were reduced 51% (P less than 0.01) and 32% (P less than 0.01), respectively. In contrast, phosphoenolpyruvate carboxykinase was unchanged. In short-term cultured hepatocytes from ethanol-fed rats, the maximum response of tyrosine amino-transferase to insulin was reduced 40% (P less than 0.01) without a change in the concentration causing 50% of the maximum response (EC50) compared with controls. In contrast, dexamethasone increased tyrosine aminotransferase to similar maximal levels and with similar EC50, indicating that ethanol did not alter the intracellular response. In conclusion, chronic ethanol ingestion caused significant time-dependent and selective changes in cell surface binding of insulin that was associated with subsequent postreceptor events.
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PMID:Impairment of hepatic insulin receptors during chronic ethanol administration. 167 84

Normal adult rat hepatocytes plated on rat tail collagen-coated dishes and fed a chemically defined medium supplemented with epidermal growth factor and dimethylsulfoxide (DMSO) were examined over a 40-d culture period for (a) the amount of albumin secreted; (b) steady-state albumin mRNA levels; (c) steady-state mRNA levels for six other liver-specific genes and three common genes; and (d)transcription of several liver-specific and common genes using isolated nuclei. DMSO-treated hepatocytes in culture for 40 d expressed albumin mRNA at 45% the level of normal liver and five other liver-specific genes at levels ranging from 21% to 72% of those in normal liver. The rate of synthesis of ligandin RNA using nuclei from 40-d hepatocytes in a nascent chain extension assay was 130% of the value obtained for normal liver, indicating that liverlike transcriptional activity for ligandin was maintained in this in vitro culture system. In contrast, the rates of synthesis of albumin and phosphoenolpyruvate carboxykinase (PepCK) mRNAs using nuclei from 40-d hepatocytes were 8% and less than 1%, respectively, and, therefore, were at levels that were much lower than was expected given the steady-state mRNA levels for these two genes. The discrepancy between the steady-state mRNA levels and rates of synthesis of RNA was analyzed, and the results suggest that the albumin and PepCK mRNAs from hepatocytes in culture may be more stable than those from liver. A plateau period for secretion of albumin, expression of albumin, alpha 1-antitrypsin, ligandin, phenylalanine hydroxylase, and PepCK mRNAs, and synthesis of albumin RNA using isolated nuclei was observed from days 6 to 40. The usefulness at a biological and molecular level of a hepatocyte culture system in which liver-specific genes are expressed over a long plateau period is discussed.
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PMID:Persistence of liver-specific messenger RNA in cultured hepatocytes: different regulatory events for different genes. 350 Sep 53

The specific performance of the adult hepatic parenchymal cell is maintained and controlled by factors deriving from the stromal bed; the chemical nature of these factors is unknown. This study aimed to develop a serum-free hierarchical hepatocyte-nonparenchymal (stromal) cell coculture system. Hepatic stromal cells proliferated on crosslinked collagen in serum-free medium with epidermal growth factor, basic fibroblast growth factor, and hepatocyte-conditioned medium; cell type composition changed during the 2-wk culture period. During the first wk, the culture consisted of proliferating sinusoidal endothelial cells with well-preserved sieve plates, proliferating hepatic stellate cells, and partially activated Kupffer cells. The number of endothelial cells declined thereafter; stellate cells and Kupffer cells became the prominent cell types after 8 d. Hepatocytes were seeded onto stromal cells precultured for 4-14 d; they adhered to stellate and Kupffer cells, but spared the islands of endothelial cells. Stellate cells spread out on top of the hepatocytes; Kupffer cell extensions established multiple contacts to hepatocytes and stellate cells. Hepatocyte viability was maintained by coculture; the positive influence of stromal cell signals on hepatocyte differentiation became evident after 48 h; a strong improvement of cell responsiveness toward hormones could be observed in cocultured hepatocytes. Hierarchial hepatocyte coculture enhanced the glucagon-dependent increases in phosphoenolpyruvate carboxykinase activity and messenger ribonucleic acid (mRNA) content three- and twofold, respectively; glucagon-activated urea production was elevated twofold. Coculturing also stimulated glycogen deposition; basal synthesis was increased by 30% and the responsiveness toward insulin and glucose was elevated by 100 and 55%, respectively. The insulin-dependent rise in the glucokinase mRNA content was increased twofold in cocultured hepatocytes. It can be concluded that long-term signals from stromal cells maintain hepatocyte differentiation. This coculture model should, therefore, provide the technical basis for the investigation of stroma-derived differentiation factors.
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PMID:Elevated expression of hormone-regulated rat hepatocyte functions in a new serum-free hepatocyte-stromal cell coculture model. 1114 49