Abstract
Glucose disposal induces a signal that modulates the transcriptional regulation of genes involved in the glycolysis and lipogenesis pathways. To investigate the role of glucose metabolism on hepatic gene expression independently from insulin action, we overexpressed glucokinase, the limiting enzyme in the glycolysis pathway, in the liver of streptozotocin-induced type 1 diabetic rats. By microarray analysis, we observed that critical genes such as liver-type pyruvate kinase, malic enzyme, fatty acid synthase, and stearoyl-CoA desaturase 1 were enhanced multiple-fold, whereas genes involved in mitochondrial fatty acid oxidation and the Krebs cycle were downregulated. Despite the increase in expression of fatty acid synthesis genes and the presence of steatosis, no major alterations to the levels of genes involved in VLDL assembly and secretion, such as diacylglycerol acyltransferases 1 and 2 and microsomal triglyceride transfer protein, were observed. Overall, our data suggest that the gene expression pattern induced by glucose metabolism favors fatty acid storage in the liver rather than secretion into the circulation.
Highlights
Glucose disposal induces a signal that modulates the transcriptional regulation of genes involved in the glycolysis and lipogenesis pathways
carbohydrate-responsive element binding protein (ChREBP) is localized in the cytoplasm under low-glucose conditions, and it translocates to the nucleus when glucose metabolism increases [9]
The aim of this study was to investigate the role of glucose on the transcriptional regulation of genes involved in de novo lipogenesis (DNL) and VLDL assembly in the liver
Summary
Glucose disposal induces a signal that modulates the transcriptional regulation of genes involved in the glycolysis and lipogenesis pathways. To investigate the role of glucose metabolism on hepatic gene expression independently from insulin action, we overexpressed glucokinase, the limiting enzyme in the glycolysis pathway, in the liver of streptozotocin-induced type 1 diabetic rats. Effects of glucose metabolism on the regulation of genes of fatty acid synthesis and triglyceride secretion in the liver. The hepatic transcription factor designated carbohydrate-responsive element binding protein (ChREBP) has been identified as a candidate for the induction of lipogenesis by glucose metabolism [8]. The aim of this study was to investigate the role of glucose on the transcriptional regulation of genes involved in DNL and VLDL assembly in the liver
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