Acute hyperglycemia normally suppresses hepatic glucose production (HGP) and gluconeogenic gene expression. Conversely, chronic hyperglycemia is accompanied by progressive increases in basal HGP and is a major contributor to hyperglycemia in both type 1 and type 2 diabetes by mechanisms that are poorly understood. The aim of this study was to investigate the molecular mechanisms whereby hypergl...

In schistosomiasis mansoni, hepatic granulomatous inflammation surrounding parasite eggs is mediated by CD4(+) T helper (Th) cells sensitized to schistosomal egg antigens (SEA). We previously showed that a prominent lymphoproliferative response of CD4(+) Th cells from schistosome-infected C57BL/6 (BL/6) mice was directed against a 62-kDa component of SEA. A partial amino acid sequence of the 62...

Zhang et al. (1) make a valuable contribution to the field of cancer metabolism, showing that the tumor suppressor p53 down-regulates the gluconeogenic key enzyme phosphoenolpyruvate carboxykinase (PEPCK, PCK1) via histone deacetylase sirtuin 6. The authors conclude that inhibition of gluconeogenesis may contribute to the tumor-suppressive function of p53. Gluconeogenesis, a reverse glycolysis ...

The decreased synthesis of hepatic phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme of gluconeogenesis, that occurs during endotoxemia was shown previously in rats to occur at the transcriptional level. In the current study, the exogenous administration of human recombinant tumor necrosis factor (TNF), a proximal mediator of endotoxic shock, reduced the PEPCK transcription ra...

The phosphoenolpyruvate carboxykinase (PEPCK) gene is regulated at the transcriptional level by a variety of effectors in a tissue-specific fashion. In order to study the parameters involved in the tissue-specific hormonal regulation of the PEPCK gene, we have used a transient expression test in well-differentiated rat hepatoma cells as well as in dedifferentiated variants. In this test, the PE...

We used an allelogenic Cre/loxP gene targeting strategy in mice to determine the role of cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in hepatic energy metabolism. Mice that lack this enzyme die within 3 days of birth, while mice with at least a 90% global reduction of PEPCK, or a liver-specific knockout of PEPCK, are viable. Surprisingly, in both cases these animals remain euglycemic af...

The gene encoding cytosolic phosphoenolpyruvate carboxykinase (GTP) [PEPCK; GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32], a key enzyme in gluconeogenesis and glyceroneogenesis, is expressed in tissues that arise from different embryonal origins: the gluconeogenic liver arises from endoderm, whereas the gluconeogenic kidney cortex and glyceroneogenic adipose tissue arise f...

The inflammatory response induced by bacterial lipopolysaccharide (LPS) has profound metabolic and physiological effects. Thus hepatic glucose production is depressed after LPS administration, which is, at least in part, due to the downregulation of phosphoenolpyruvate carboxykinase (PEPCK) expression. PEPCK is a key regulatory enzyme of the gluconeogenic pathway. Expression of heat shock prote...

Cyclic AMP-response element modulator alpha (CREMalpha) is a transcription factor that is highly related to cAMP-response element-binding protein (CREB) but represses cAMP-induced gene expression from simple artificial promoters containing a cAMP-response element (CRE). CREMalpha lacks two glutamine-rich Q regions that, in CREB, are thought to be necessary for transcriptional activation. Nevert...