Bilirubin has potent biological beneficial effects, protecting against atherosclerosis, obesity, and metabolic syndrome. The aim of this study was to assess serum bilirubin concentrations and (TA)n and (GT)n microsatellite variations in the promoter regions of the UGT1A1 and HMOX1 genes, respectively, in patients with type 2 diabetes mellitus (T2DM). The study was carried out in 220 patients with T2DM and 231 healthy control subjects, in whom standard biochemical tests were performed. The (TA)n and (GT)n dinucleotide variations were determined by means of fragment (size-based) analysis using an automated capillary DNA sequencer. Compared to controls, both male and female patients with T2DM had lower serum bilirubin concentrations (9.9 vs. 12.9 μmol/L, and 9.0 vs. 10.6 μmol/L, in men and women, respectively, p < 0.001). Phenotypic Gilbert syndrome was much less prevalent in T2DM patients, as was the frequency of the (TA)7/7UGT1A1 genotype in male T2DM patients. (GT)nHMOX1 genetic variations did not differ between diabetic patients and controls. Our results demonstrate that the manifestation of T2DM is associated with lower serum bilirubin concentrations. Consumption of bilirubin due to increased oxidative stress associated with T2DM seems to be the main explanation, although (TA)n repeat variations in UGT1A1 partially contribute to this phenomenon.

• Klíčová slova
• Gilbert syndrome, HMOX1, UGT1A1, benign hyperbilirubinemia, bilirubin, heme oxygenase, type 2 diabetes mellitus,
• MeSH
• bilirubin metabolismus   MeSH
• diabetes mellitus 2. typu * genetika   MeSH
• genotyp MeSH
• glukuronosyltransferasa genetika   metabolismus   MeSH
• hemoxygenasa-1 genetika   metabolismus   MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• promotorové oblasti (genetika) MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• bilirubin MeSH
• glukuronosyltransferasa MeSH
• hemoxygenasa-1 MeSH
• HMOX1 protein, human MeSH Prohlížeč

Bilirubin has several physiological functions, both beneficial and harmful. In addition to reactive oxygen species-scavenging activities, bilirubin has potent immunosuppressive effects associated with long-term pathophysiological sequelae. It has been recently recognized as a hormone with endocrine actions and interconnected effects on various cellular signaling pathways. Current studies show that bilirubin also decreases adiposity and prevents metabolic and cardiovascular diseases. All in all, the physiological importance of bilirubin is only now coming to light, and strategies for increasing plasma bilirubin levels to combat chronic diseases are starting to be considered. This review discusses the beneficial effects of increasing plasma bilirubin, incorporates emerging areas of bilirubin biology, and provides key concepts to advance the field.

• Klíčová slova
• BVRA, Blvra, HO-1, Hmox1, bilirubin, cardiovascular disease, cell signaling, heme oxygenase, metabolism, nuclear receptors,
• MeSH
• bilirubin * metabolismus   farmakologie   MeSH
• hemoxygenasa-1 metabolismus   MeSH
• kardiovaskulární nemoci * MeSH
• lidé MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• bilirubin * MeSH
• hemoxygenasa-1 MeSH
• reaktivní formy kyslíku MeSH