Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.27 (AMPK)
 6,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PFK-2/FBPase-2 (6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase) catalyses the formation and degradation of fructose 2,6-P(2) (fructose 2,6-bisphosphate) and is also a glucokinase-binding protein. The role of fructose 2,6-P(2) in regulating glucose metabolism and insulin secretion in pancreatic beta-cells is unresolved. We down-regulated the endogenous isoforms of PFK-2/FBPase-2 with siRNA (small interfering RNA) and expressed KA (kinase active) and KD (kinase deficient) variants to distinguish between the role of PFK-2/FBPase-2 protein and the role of its product, fructose 2,6-P(2), in regulating beta-cell function. Human islets expressed the PFKFB2 (the gene encoding isoform 2 of the PFK2/FBPase2 protein) and PFKFB3 (the gene encoding isoform 3 of the PFK2/FBPase2 protein) isoforms and mouse islets expressed PFKFB2 at the mRNA level [RT-PCR (reverse transcription-PCR)]. Rat islets expressed PFKFB2 lacking the C-terminal phosphorylation sites. The glucose-responsive MIN6 and INS1E cell lines expressed PFKFB2 and PFKFB3. PFK-2 activity and the cell content of fructose 2,6-P(2) were increased by elevated glucose concentration and during pharmacological activation of AMPK (AMP-activated protein kinase), which also increased insulin secretion. Partial down-regulation of endogenous PFKFB2 and PFKFB3 in INS1E by siRNA decreased PFK-2/FBPase-2 protein, fructose 2,6-P(2) content, glucokinase activity and glucoseinduced insulin secretion. Selective down-regulation of glucose-induced fructose 2,6-P(2) in the absence of down-regulation of PFK-2/FBPase-2 protein, using a KD PFK-2/FBPase-2 variant, resulted in sustained glycolysis and elevated glucose-induced insulin secretion, indicating an over-riding role of PFK-2/FBPase-2 protein, as distinct from its product fructose 2,6-P(2), in potentiating glucose-induced insulin secretion. Whereas down-regulation of PFK-2/FBPase-2 decreased glucokinase activity, overexpression of PFK-2/FBPase-2 only affected glucokinase distribution. It is concluded that PFK-2/FBPase-2 protein rather than its product fructose 2,6-P(2) is the over-riding determinant of glucose-induced insulin secretion through regulation of glucokinase activity or subcellular targeting.
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PMID:A role for PFK-2/FBPase-2, as distinct from fructose 2,6-bisphosphate, in regulation of insulin secretion in pancreatic beta-cells. 1803 79

We aimed to identify potential mechanism associated with acute kidney injury (AKI) after kidney transplantation. The dataset GSE53771, which contained 18 zero-hour (ZERO group) and 18 selected post-transplant (POST group) biopsy samples from 18 kidney allografts (8 AKI and 10 controls) was downloaded from GEO database. Differentially expressed miRNAs (DEMIs) were screened using limma package, and bidirectional hierarchical clustering of the DEMIs was performed using the pheatmap package. Target genes of DEMIs were predicted by miRWalk 2.0, miRNA-target genes networks were presented using Cytoscape, protein-protein interaction (PPI) networks were constructed by STRING (version:10.0) database, and competing endogenous RNAs (ceRNA) regulating network were constructed using Cytoscape. In ZERO and POST groups, a total of 4 and 24 differentially expressed miRNAs were obtained in AKI samples compared with control, respectively. Specifically, 71 lncRNAs were obtained to interact with five miRNAs (hsa-miR-215-5p, hsa-miR-192-5p, hsa-miR-422a, hsa-miR-212-3p and hsa-miR-122-5p). Histone chaperone ASF1A (ASF1A) and bromodomain and WD repeat-containing protein 1(BRWD1) were targeted by hsa-miR-212-3p in PPI network. In ceRNA network, lncRNA XIST could interact with four miRNAs (hsa-miR-212-3p, hsa-miR-122-5p, hsa-miR-215-5p, and hsa-miR-192-5p). LncRNA XIST might serve as a ceRNA to sponge hsa-miR-212-3p to regulate the development of AKI via altering the expression of ASF1A/BRWD1. Furthermore, lncRNA XIST could also interact with hsa-miR-122-5p to modulate the expression of PFKFB2 in thyroid hormone signaling pathway and AMPK signaling pathway. LncRNA XIST can serve as a ceRNA to sponge hsa-miR-212-3p and hsa-miR-122-5p to regulate AKI progression via modulating the expression of ASF1A, BRWD1, and PFKFB2.[Figure: see text].
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PMID:LncRNA XIST serves as a ceRNA to regulate the expression of ASF1A, BRWD1M, and PFKFB2 in kidney transplant acute kidney injury via sponging hsa-miR-212-3p and hsa-miR-122-5p. 3191 81