Bradykinin B2 Receptor Signaling Increases Glucose Uptake and Oxidation: Evidence and Open Questions
The Kinin B2 receptor (B2R) is classically involved in vasodilation and inflammatory responses. However, through the observation of hypoglycemic effects of Angiotensin-I-Converting Enzyme (ACE) inhibitors, this protein has been related to metabolic glucose modulation in physiological and pathophysio...
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.01162/full |
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| author | Marcos Fernandes Gregnani Marcos Fernandes Gregnani Talita G. Hungaro Talita G. Hungaro Leonardo Martins-Silva Michael Bader Michael Bader Michael Bader Michael Bader Ronaldo C. Araujo |
| author_facet | Marcos Fernandes Gregnani Marcos Fernandes Gregnani Talita G. Hungaro Talita G. Hungaro Leonardo Martins-Silva Michael Bader Michael Bader Michael Bader Michael Bader Ronaldo C. Araujo |
| author_sort | Marcos Fernandes Gregnani |
| collection | DOAJ |
| description | The Kinin B2 receptor (B2R) is classically involved in vasodilation and inflammatory responses. However, through the observation of hypoglycemic effects of Angiotensin-I-Converting Enzyme (ACE) inhibitors, this protein has been related to metabolic glucose modulation in physiological and pathophysiological contexts. Although several studies have evaluated this matter, the different methodologies and models employed, combined with the distinct target organs, results in a challenge to summarize and apply the knowledge in this field. Therefore, this review aims to compile human and animal data in order to provide a big picture about what is already known regarding B2R and glucose metabolism, as well to suggest pending investigation issues aiming at evaluating the role of B2R in relation to glucose metabolism in homeostatic situations and metabolic disturbances. The data indicate that B2R signaling is involved mainly in glucose uptake in skeletal muscle and adipose tissue, acting as a synergic player beside insulin. However, most data indicate that B2R induces increased glucose oxidation, instead of storage, via activation of a broad signaling cascade involving Nitric Oxide (NO) and cyclic-GMP dependent protein kinase (PKG). Additionally, we highlight that this modulation is impaired in metabolic disturbances such as diabetes and obesity, and we provide a hypothetic mechanism to explain this blockade in light of literature data provided for this review, as well as other authors. |
| first_indexed | 2024-12-14T02:02:47Z |
| format | Article |
| id | doaj.art-90b2a6c461a9489cbd7b9199357e70f0 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-14T02:02:47Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-90b2a6c461a9489cbd7b9199357e70f02022-12-21T23:20:58ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-08-011110.3389/fphar.2020.01162536136Bradykinin B2 Receptor Signaling Increases Glucose Uptake and Oxidation: Evidence and Open QuestionsMarcos Fernandes Gregnani0Marcos Fernandes Gregnani1Talita G. Hungaro2Talita G. Hungaro3Leonardo Martins-Silva4Michael Bader5Michael Bader6Michael Bader7Michael Bader8Ronaldo C. Araujo9Laboratory of Genetic and Metabolism of Exercise, Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, BrazilMax-Delbrück Center for Molecular Medicine (MDC), Berlin, GermanyLaboratory of Genetic and Metabolism of Exercise, Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, BrazilMax-Delbrück Center for Molecular Medicine (MDC), Berlin, GermanyMax-Delbrück Center for Molecular Medicine (MDC), Berlin, GermanyMax-Delbrück Center for Molecular Medicine (MDC), Berlin, GermanyInstitute for Biology, University of Lübeck, Lübeck, GermanyCharité University Medicine, Berlin, GermanyGerman Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, GermanyLaboratory of Genetic and Metabolism of Exercise, Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, BrazilThe Kinin B2 receptor (B2R) is classically involved in vasodilation and inflammatory responses. However, through the observation of hypoglycemic effects of Angiotensin-I-Converting Enzyme (ACE) inhibitors, this protein has been related to metabolic glucose modulation in physiological and pathophysiological contexts. Although several studies have evaluated this matter, the different methodologies and models employed, combined with the distinct target organs, results in a challenge to summarize and apply the knowledge in this field. Therefore, this review aims to compile human and animal data in order to provide a big picture about what is already known regarding B2R and glucose metabolism, as well to suggest pending investigation issues aiming at evaluating the role of B2R in relation to glucose metabolism in homeostatic situations and metabolic disturbances. The data indicate that B2R signaling is involved mainly in glucose uptake in skeletal muscle and adipose tissue, acting as a synergic player beside insulin. However, most data indicate that B2R induces increased glucose oxidation, instead of storage, via activation of a broad signaling cascade involving Nitric Oxide (NO) and cyclic-GMP dependent protein kinase (PKG). Additionally, we highlight that this modulation is impaired in metabolic disturbances such as diabetes and obesity, and we provide a hypothetic mechanism to explain this blockade in light of literature data provided for this review, as well as other authors.https://www.frontiersin.org/article/10.3389/fphar.2020.01162/fullbradykininkinin B2 receptorglucoseuptakeoxidationmetabolism |
| spellingShingle | Marcos Fernandes Gregnani Marcos Fernandes Gregnani Talita G. Hungaro Talita G. Hungaro Leonardo Martins-Silva Michael Bader Michael Bader Michael Bader Michael Bader Ronaldo C. Araujo Bradykinin B2 Receptor Signaling Increases Glucose Uptake and Oxidation: Evidence and Open Questions Frontiers in Pharmacology bradykinin kinin B2 receptor glucose uptake oxidation metabolism |
| title | Bradykinin B2 Receptor Signaling Increases Glucose Uptake and Oxidation: Evidence and Open Questions |
| title_full | Bradykinin B2 Receptor Signaling Increases Glucose Uptake and Oxidation: Evidence and Open Questions |
| title_fullStr | Bradykinin B2 Receptor Signaling Increases Glucose Uptake and Oxidation: Evidence and Open Questions |
| title_full_unstemmed | Bradykinin B2 Receptor Signaling Increases Glucose Uptake and Oxidation: Evidence and Open Questions |
| title_short | Bradykinin B2 Receptor Signaling Increases Glucose Uptake and Oxidation: Evidence and Open Questions |
| title_sort | bradykinin b2 receptor signaling increases glucose uptake and oxidation evidence and open questions |
| topic | bradykinin kinin B2 receptor glucose uptake oxidation metabolism |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.01162/full |
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