A novel role of bone morphogenetic protein 6 (BMP6) in glucose homeostasis.

Autor: Pauk M; Laboratory of Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Salata 11, Zagreb, Croatia., Bordukalo-Niksic T; Laboratory of Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Salata 11, Zagreb, Croatia., Brkljacic J; Laboratory of Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Salata 11, Zagreb, Croatia., Paralkar VM; Pfizer Inc, Groton, CT, USA., Brault AL; Pfizer Inc, Groton, CT, USA., Dumic-Cule I; Laboratory of Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Salata 11, Zagreb, Croatia., Borovecki F; Department for Functional Genomics, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Salata 2, Zagreb, Croatia., Grgurevic L; Laboratory of Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Salata 11, Zagreb, Croatia., Vukicevic S; Laboratory of Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Salata 11, Zagreb, Croatia. slobodan.vukicevic@mef.hr.
Jazyk: angličtina
Zdroj: Acta diabetologica [Acta Diabetol] 2019 Mar; Vol. 56 (3), pp. 365-371. Date of Electronic Publication: 2018 Dec 11.
DOI: 10.1007/s00592-018-1265-1
Abstrakt: Aims: Bone morphogenetic proteins (BMPs) are involved in the development and homeostasis of multiple organs and tissues. There has been a significant focus on understanding the role of BMPs in pancreatic β-cell dysfunction associated with type 2 diabetes (T2D). Our objective was to investigate the relationship between BMP6 and glucose homeostasis.
Methods: Ob/ob mice were treated with BMP6 for 6 days and analyzed for insulin release, body weight, lipid parameters and glucose tolerance. Quantitative real-time PCR, chromatin immunoprecipitation and glucose output assays were used to assess BMP6 effect on gluconeogenesis in rat hepatoma H4IIE cells. Specificity of BMP6 receptors was characterized by the utilization of various receptor Fc fusion proteins in luciferase reporter gene and glucose output assays in INS1 and H4IIE cells.
Results: Treatment of ob/ob mice with BMP6 for 6 days resulted in a reduction of circulating glucose and lipid levels, followed by a significantly elevated plasma insulin level in a dose-dependent manner. In addition, BMP6 improved the glucose excursion during an oral glucose tolerance test, lowering the total glycemic response by 21%. In rat H4IIE hepatoma cells, BMP6 inhibited gluconeogenesis and glucose output via downregulation the PepCK expression. Moreover, BMP6 inhibited glucose production regardless of the presence of cAMP, antagonizing its glycogenolytic effect. BMP6 acted on pancreatic and liver cells utilizing Alk3, Alk6 and ActRIIA serine/threonine kinase receptors.
Conclusions: Collectively, we demonstrate that BMP6 improves glycaemia in T2D mice and regulates glucose metabolism in hepatocytes representing an exciting prospect for future treatments of diabetes.
Databáze: MEDLINE
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