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)

Akt is critical in insulin-induced metabolism of glucose and lipids. To investigate functions induced by hepatic Akt activation, a constitutively active Akt, NH(2)-terminally myristoylation signal-attached Akt (myr-Akt), was overexpressed in the liver by injecting its adenovirus into mice. Hepatic myr-Akt overexpression resulted in a markedly hypoglycemic, hypoinsulinemic, and hypertriglyceridemic phenotype with fatty liver and hepatomegaly. To elucidate the sterol regulatory element binding protein (SREBP)-1c contribution to these phenotypic features, myr-Akt adenovirus was injected into SREBP-1 knockout mice. myr-Akt overexpression induced hypoglycemia and hepatomegaly with triglyceride accumulation in SREBP-1 knockout mice to a degree similar to that in normal mice, whereas myr-Akt-induced hypertriglyceridemia in knockout mice was milder than that in normal mice. The myr-Akt-induced changes in glucokinase, phosphofructokinase, glucose-6-phosphatase, and PEPCK expressions were not affected by knocking out SREBP-1, whereas stearoyl-CoA desaturase 1 induction was completely inhibited in knockout mice. Constitutively active SREBP-1-overexpressing mice had fatty livers without hepatomegaly, hypoglycemia, or hypertriglyceridemia. Hepatic acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase 1, and glucose-6-phosphate dehydrogenase expressions were significantly increased by overexpressing SREBP-1, whereas glucokinase, phospho-fructokinase, glucose-6-phosphatase, and PEPCK expressions were not or only slightly affected. Thus, SREBP-1 is not absolutely necessary for the hepatic Akt-mediated hypoglycemic effect. In contrast, myr-Akt-induced hypertriglyceridemia and hepatic triglyceride accumulation are mediated by both Akt-induced SREBP-1 expression and a mechanism involving fatty acid synthesis independent of SREBP-1.
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PMID:Hepatic Akt activation induces marked hypoglycemia, hepatomegaly, and hypertriglyceridemia with sterol regulatory element binding protein involvement. 1463 50

The high-fat diet (HFD)-fed mouse is a model of obesity, impaired glucose tolerance, and insulin resistance. The main objective of this study was to elucidate the molecular mechanisms underlying the antidiabetogenic and weight-lowering effects of 17beta-estradiol (E(2)) in this mouse model. C57BL/6 female mice (8 wk old) were fed on a HFD for 10 mo. E(2), given daily (50 microg/kg s.c.) during the last month of feeding, decreased body weight and markedly improved glucose tolerance and insulin sensitivity. Plasma levels of insulin, leptin, resistin, and adiponectin were decreased. We demonstrated that E(2) treatment decreased the expression of genes encoding resistin and leptin in white adipose tissue (WAT), whereas adiponectin expression was unchanged. Furthermore, in WAT we demonstrated decreased expression levels of sterol regulatory element-binding protein 1c (SREBP1c) and its lipogenic target genes, such as fatty acid synthase and stearoyl-CoA desaturase 1 (SCD1). In the liver, the expression levels of transcription factors such as liver X receptor alpha and SREBP1c were not changed by E(2) treatment, but the expression of the key lipogenic gene SCD1 was reduced. This was accompanied by decreased hepatic triglyceride content. Importantly, E(2) decreased the hepatic expression of glucose-6-phosphatase (G-6-Pase). We conclude that E(2) treatment exerts antidiabetic and antiobesity effects in HFD mice and suggest that this is related to decreased expression of lipogenic genes in WAT and liver and suppression of hepatic expression of G-6-Pase. Decreased plasma levels of resistin probably also play an important role in this context.
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PMID:Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice. 1869 13

n-3 highly unsaturated fatty acids (n-3 HUFAs) have been shown to suppress lipid accumulation and improve protein utilization in grass carp; however, little is known about the underlying molecular mechanism. Hence, we analyzed the hepatopancreas transcriptome of grass carp (Ctenopharyngodon idellus) fed either lard oil (LO) or fish oil (FO) diets. RNA-seq data showed that 125 genes were significantly up-regulated and 107 were significantly down-regulated in the FO group. Among them, 17 lipid metabolism related genes, 12 carbohydrate metabolism related genes, and 34 protein metabolism related genes were selected. Lipid metabolism related genes, such as very long-chain acyl-CoA synthetase (ACSVL),carnitine O-palmitoyltransferase 1 (CPT1) and carnitine-acylcarnitine translocase (CACT), were up-regulated in the FO group. But the genes of diacylglycerol O-acyltransferase 2 (DGAT2) and stearoyl-CoA desaturase (SCD) were down-regulated. Down-regulation of glycolysis related genes, such as 6-phosphofructokinase (PFK), phosphoglycerate kinase (PGK) and pyruvate dehydrogenase kinase (PDK), added with up-regulation of gluconeogenesis related genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), suggests lower utilization of carbohydrate of the FO group. Besides, dietary FO also influenced the protein metabolism related genes, such as up-regulation of genes involved in digestion of dietary protein, mRNA transcription, protein translation and amino acid utilization, down-regulation of genes involved in mRNA degradation and ubiquitination of protein. Interestingly, the up-regulation of mitochondrial uncoupling protein 2 (UCP2) and down-regulation of oxidative phosphorylation related genes (cytochrome c oxidase subunit 4 isoform 2 [COX4I2], HIG1 domain family member 1A [HIGD1A] and cytochrome-b5 reductase [CYB5R]) suggest that energy metabolism may be also influenced by dietary fatty acid composition. These findings presented here provide a comprehensive understanding of the molecular mechanisms governing the effects of fish oil in grass carp.
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PMID:Comparative analysis of the hepatopancreas transcriptome of grass carp (Ctenopharyngodon idellus) fed with lard oil and fish oil diets. 2586

The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance along with obesity. 6,7-dimethylesculetin (DE) is an active component of Yin Zhi Huang which is a traditional Asian medicine used to treat neonatal jaundice via CAR. In this study, we examined whether DE could affect the expression of gluconeogenic and lipogenic genes via human CAR pathway using human HepG2 cells in vitro. We also studied whether DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in high-fat diet (HFD)-induced obese pregnant mice. Dimethylesculetin suppressed the mRNA expression of gluconeogenic genes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, and lipogenic genes, sterol regulatory element-binding protein 1 and stearoyl-CoA desaturase 1, and enhanced CAR-mediated transcription. Blocking the CAR-mediated pathway abolished the effect of DE in vitro. DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in HFD-induced obese pregnant mice in vivo. Our data indicate that DE might be a potential therapeutic agent for obese pregnant patients with insulin resistance through CAR to prevent the perinatal outcomes such as preeclampsia, gestational diabetes, and macrosomia. Further analysis of possible complications and side effects using animal models is required.
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PMID:Dimethylesculetin ameliorates maternal glucose intolerance and fetal overgrowth in high-fat diet-fed pregnant mice via constitutive androstane receptor. 2742 90

Our team has previously demonstrated that Ganoderma lucidum polysaccharides F31 have hypoglycemic effects on diabetic mice. This study provides insight into the system-level hypoglycemic mechanisms of F31 by the integrative analysis of transcriptomics and proteomics data. To explore the omics perspective for the mechanisms of action, the protein and gene expression in the liver from the normal control (NC), diabetic db/db control mice (DC) and F31-treated db/db mice (F31) were analyzed by iTRAQ and RNA-Seq. The differential expression proteins (DEPs) and differential expression genes (DEGs) were analyzed based on their gene ontology (GO) annotations and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and the expression of DEGs and DEPs was verified by quantitative polymerase chain reaction (qPCR) and western blotting (WB). We identified sixty-five DEGs and sixty-two DEPs in the F31-treated group as compared with the DC. Integrated analysis of the RNA-Seq data and proteomics data indicated that the two DEGs/DEPs-Gck [glucokinase (GCK)] and Cyp4a12a [cytochrome P450, family 4, subfamily a, polypeptide 12a (CYP4A12A)]-showed the same trend in mRNA and protein expression levels in the comparison of F31-VS-DC. KEGG analysis revealed that the peroxisome proliferator-activated receptors (PPARs) signaling pathway was enriched in both of the comparisons of NC-VS-DC and F31-VS-DC at the protein expression level. In the analysis of the gene and protein expression of candidate proteins targeting diabetes, we found that three genes [Gck, glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK)] and three proteins [GCK, glucose transporter type 2 (GLUT2), pyruvate kinase (PYK) ] in the glycolysis and gluconeogenesis pathways, proteins of the Janus-activated kinase 2 (JAK2) in the insulin pathway, and two genes [Cyp4a12a and stearoyl-CoA desaturase 2 (SCD2)] in the lipid metabolism were expressed significantly differently in the F31-treated group as compared with the DC group, which played important roles in the hypoglycemic activity of F31. Cluster analysis demonstrated that microRNAs probably participated in the regulation of the genes involved the glucose metabolism. These results provide theoretical evidence for F31 as a potential functional food ingredient for the prevention and treatment of type 2 diabetes.
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PMID:Hypoglycemic mechanisms of Ganoderma lucidum polysaccharides F31 in db/db mice via RNA-seq and iTRAQ. 3046 64