Biliverdin reductase-A protein levels are reduced in type 2 diabetes and are associated with poor glycometabolic control
| Autor: | Ilaria Zuliani, Anna Reale, Sara Dule, Michele Zampieri, Marco Giorgio Baroni, Laura Bertoccini, Flavia Agata Cimini, Sara Pagnotta, Eugenio Barone, Maria Gisella Cavallo, Ilaria Barchetta |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Blood Glucose
Male Oxidoreductases Acting on CH-CH Group Donors medicine.medical_specialty endocrine system diseases Type 2 diabetes General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Internal medicine Diabetes Mellitus medicine Humans Glucose homeostasis glucose homeostasis metabolic disorders General Pharmacology Toxicology and Pharmaceutics Heme Aged Biliverdin business.industry Biliverdin reductase-A Heme oxygenase Inflammation Metabolic disorders Diabetes Mellitus Type 2 Female Heme Oxygenase-1 Logistic Models Middle Aged Multivariate Analysis heme oxygenase inflammation type 2 diabetes Biliverdin reductase nutritional and metabolic diseases General Medicine medicine.disease Endocrinology chemistry Glycated hemoglobin business Type 2 Lipoprotein |
| Popis: | Aim Biliverdin reductase-A (BVR-A) other than its canonical role in the degradation pathway of heme as partner of heme oxygenase-1 (HO1), has recently drawn attention as a protein with pleiotropic functions involved in insulin-glucose homeostasis. However, whether BVR-A expression is altered in type 2 diabetes (T2D) has never been evaluated. Main methods BVR-A protein levels were evaluated in T2D (n = 44) and non-T2D (n = 29) subjects, who underwent complete clinical workup and routine biochemistry. In parallel, levels HO1, whose expression is regulated by BVR-A as well as levels of tumor necrosis factor α (TNFα), which is a known repressor for BVR-A with pro-inflammatory properties, were also assessed. Key findings BVR-A levels were significantly lower in T2D subjects than in non-T2D subjects. Reduced BVR-A levels were associated with greater body mass, systolic blood pressure, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), triglycerides, transaminases and TNFα, and with lower high-density lipoprotein (HDL) levels. Lower BVR-A levels are associated with reduced HO1 protein levels and the multivariate analysis showed that BVR-A represented the main determinant of HO1 levels in T2D after adjustment. In addition, reduced BVR-A levels were able to predict the presence of T2D with AUROC = 0.69. for potential confounders. Significance Our results demonstrate for the first time that BVR-A protein levels are reduced in T2D individuals, and that this alteration strictly correlates with poor glycometabolic control and a pro-inflammatory state. Hence, these observations reinforce the hypothesis that reduced BVR-A protein levels may represent a key event in the dysregulation of intracellular pathways finally leading to metabolic disorders. |
| Databáze: | OpenAIRE |
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