Kinin B1 receptor modulates glucose homeostasis and physical exercise capacity by altering adrenal catecholamine synthesis and secretion

• Published in: Molecular and cellular endocrinology 2024-01, Vol.579, p.112085-112085, Article 112085
• Main Authors: Fernandes Gregnani, Marcos, Budu, Alexandre, Batista, Rogério Oliveira, Ornellas, Fábio Henrique, Estrela, Gabriel Rufino, Arruda, Adriano Cleis, Freitas Lima, Leandro Ceotto, Kremer, Jean Lucas, Favaroni Mendes, Lys Angela, Casarini, Dulce Elena, Lotfi, Claudimara Ferini Pacicco, Oyama, Lila Missae, Bader, Michael, Araújo, Ronaldo Carvalho
• Format: Article
• Language: English
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2023.112085

Our group has shown in several papers that kinin B1 receptor (B1R) is involved in metabolic adaptations, mediating glucose homeostasis and interfering in leptin and insulin signaling. Since catecholamines are involved with metabolism management, we sought to evaluate B1R role in catecholamine synthesis/secretion. Using B1R global knockout mice, we observed increased basal epinephrine content, accompanied by decreased hepatic glycogen content and increased glucosuria. When these mice were challenged with maximal intensity exercise, they showed decreased epinephrine and norepinephrine response, accompanied by disturbed glycemic responses to effort and poor performance. This phenotype was related to alterations in adrenal catecholamine synthesis: increased basal epinephrine concentration and reduced norepinephrine content in response to exercise, as well decreased gene expression and protein content of tyrosine hydroxylase and decreased gene expression of dopamine beta hydroxylase and kinin B2 receptor. We conclude that the global absence of B1R impairs catecholamine synthesis, interfering with glucose metabolism at rest and during maximal exercise.