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.

Biliverdin reductase-A protein levels are reduced in type 2 diabetes and are associated with poor glycometabolic control / Cimini, F. A.; Barchetta, I.; Zuliani, I.; Pagnotta, S.; Bertoccini, L.; Dule, S.; Zampieri, M.; Reale, A.; Baroni, M. G.; Cavallo, M. G.; Barone, E.. - In: LIFE SCIENCES. - ISSN 0024-3205. - 284:(2021), p. 119913. [10.1016/j.lfs.2021.119913]

Biliverdin reductase-A protein levels are reduced in type 2 diabetes and are associated with poor glycometabolic control

Cimini F. A.;Barchetta I.;Zuliani I.;Pagnotta S.;Bertoccini L.;Dule S.;Zampieri M.;Reale A.;Baroni M. G.;Cavallo M. G.;Barone E.
2021

Abstract

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.
2021
Biliverdin reductase-A; glucose homeostasis; heme oxygenase; inflammation; metabolic disorders; type 2 diabetes
01 Pubblicazione su rivista::01a Articolo in rivista
Biliverdin reductase-A protein levels are reduced in type 2 diabetes and are associated with poor glycometabolic control / Cimini, F. A.; Barchetta, I.; Zuliani, I.; Pagnotta, S.; Bertoccini, L.; Dule, S.; Zampieri, M.; Reale, A.; Baroni, M. G.; Cavallo, M. G.; Barone, E.. - In: LIFE SCIENCES. - ISSN 0024-3205. - 284:(2021), p. 119913. [10.1016/j.lfs.2021.119913]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1573343
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