Disease relevance of Pbef1

• Because renal failure per se is associated with both increased levels of circulating peptides and marked insulin resistance, even in the absence of diabetes mellitus, we hypothesized that visfatin could be a factor linking inflammation, kidney disease, and insulin resistance in this patient group [1].
• Although these data confirm an involvement of PBEF in disease progression, the consequence of its action remains to be determined [2].
• Synovial fluid levels of PBEF were significantly higher in RA patients than in osteoarthritis patients [2].
• Recently, a bacterial protein encoded by nadV, a gene from the prokaryote Haemophilus ducreyi displaying significant homology with PBEF, has been identified as a nicotinamide phosphoribosyltranferase (NAmPRTase), an enzyme involved in nicotinamide adenine dinucleotide (NAD) biosynthesis [3].
• In patients with inflammatory bowel disease, plasma levels of visfatin are elevated and its mRNA expression is significantly increased in colonic tissue of Crohn's and ulcerative colitis patients compared with healthy controls [4].

High impact information on Pbef1

• Visfatin-stimulated monocytes show augmented FITC-dextran uptake and an enhanced capacity to induce alloproliferative responses in human lymphocytes [4].
• In CD14(+) monocytes, visfatin induces the production of IL-1beta, TNF-alpha, and especially IL-6 [4].
• In this study, we show that recombinant visfatin activates human leukocytes and induces cytokine production [4].
• Macrophages, dendritic cells, and colonic epithelial cells might be additional sources of visfatin as determined by confocal microscopy [4].
• Analysis of human RA synovial tissue confirmed that PBEF immunolocalized in apical synovial membrane cells, endothelial cells, adipocytes, and lymphoid aggregates [2].

Biological context of Pbef1

• However, there were no significant differences between patients with and without diabetes, and the significant differences in circulating visfatin levels between genotypes disappeared after adjustment for differences in age, sex, GFR, and serum albumin level [1].
• Gene expression profiling with oligonucleotide microarrays also demonstrated a significant correlation between the expression profiles of Nampt- and Sir2alpha-overexpressing cells [5].
• Increased dosage of Nampt, but not Nmnat, increased the total cellular NAD level and enhanced the transcriptional regulatory activity of the catalytic domain of Sir2alpha recruited onto a reporter gene in mouse fibroblasts [5].
• We genotyped two PBEF single-nucleotide polymorphisms (SNPs) in a well characterized sample of white patients with sepsis-associated ALI, patients with severe sepsis, and healthy subjects and observed that carriers of the haplotype GC from SNPs T-1001G and C-1543T had a 7.7-fold higher risk of ALI (95% confidence interval 3.01-19.75, p < 0.001) [6].
• Taken together, our results show a differential regulation of visfatin mRNA by insulin resistance-inducing hormones, supporting the view that this adipo-cytokine might be an interesting novel candidate linking core components of the metabolic syndrome such as obesity and insulin resistance [7].

Anatomical context of Pbef1

• BACKGROUND: Visfatin, also known as pre-B-cell colony-enhancing factor 1 (PBEF-1), recently was shown to be secreted from adipocytes and have insulin-mimetic properties in mice [1].
• Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis [3].
• The murine homologue of the previously identified human "pre-B-cell colony-enhancing factor" (PBEF) gene coding for a putative cytokine has been identified by screening a subtractive library enriched in genes expressed in activated T lymphocytes [3].
• Visfatin: a protein secreted by visceral fat that mimics the effects of insulin [8].
• Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice [8].

Associations of Pbef1 with chemical compounds

• Using a panel of antibodies to murine PBEF, we demonstrate in this work that, similarly to its microbial counterpart, the murine protein is a NAmPRTase, catalyzing the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD [3].
• Taken together, our study suggests that IL-6 might influence glucose tolerance in part by regulation of the novel insulin-mimetic adipocytokine visfatin [9].
• In contrast, troglitazone did not reverse the negative effect of IL-6 on visfatin synthesis under these conditions [9].
• Interestingly, 100 nM dexamethasone significantly increased visfatin mRNA by almost 1.5-fold [7].
• In contrast, 500 ng/ml growth hormone (GH), 10 ng/ml tumor necrosis factor (TNF) alpha, and 10 microM isoproterenol downregulated visfatin expression by 45%, 36%, and 43% respectively [7].

Regulatory relationships of Pbef1

• Interestingly, 30 ng/ml IL-6 time-dependently downregulated visfatin synthesis with a significant 40% suppression seen after 4 h of treatment [9].

Other interactions of Pbef1

• These findings suggest that NAD biosynthesis mediated by Nampt regulates the function of Sir2alpha and thereby plays an important role in controlling various biological events in mammals [5].

Analytical, diagnostic and therapeutic context of Pbef1

• Serum visfatin was measured by using commercially available enzyme-linked immunosorbent assay, and we also performed genotyping of 3 verified polymorphisms in the visfatin gene (-423A/G, -1001T/G, and -1535C/T) [1].
• Synovial levels of PBEF were quantified by enzyme immunoassay [2].
• PBEF and STAT were detected by immunohistochemistry, immunoblotting, and electrophoretic mobility shift assay [2].
• Expression profiling in animal models of ALI (canine and murine) and human ALI detected significant expression of pre-B-cell colony-enhancing factor (PBEF), a gene not previously associated with lung pathophysiology [6].
• To clarify expression and regulation of this adipocytokine, visfatin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction in 3T3-L1 adipocytes during adipogenesis and after treatment with various hormones known to alter insulin sensitivity [7].

References