Investigação dos mecanismos de ação hipoglicemiante do extrato bruto das folhas de myrcia bella cambess. em fígado, músculo esquelético e tecido adiposo em modelo de diabetes tipo 1 por estreptozotocina
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Data
2017-02-16
Autores
Vareda, Priscilla Maria Ponce
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O Diabetes mellitus (DM) é uma desordem metabólica caracterizada por hiperglicemia decorrente de defeitos na secreção ou ação da insulina, que acarreta distúrbios no metabolismo de carboidratos, lipídeos e proteínas. A incidência do DM aumenta de maneira alarmante em todo o mundo e os estudos com plantas que possuam efeitos antidiabéticos despertam cada vez mais o interesse por parte de pesquisadores. Em resultados anteriores, observamos que camundongos induzidos por estreptozotocina exibiram melhora no quadro diabético após serem submetidos ao tratamento com extrato bruto das folhas de Myrcia bella. Neste trabalho, decidimos avaliar os mecanismos moleculares envolvidos nos processos de captação e armazenamento de glicose em tecidos periféricos como fígado, músculo esquelético e tecido adiposo neste modelo experimental. No mais, procuramos avaliar a atividade inibitória in vitro e in vivo do extrato de M. bella sobre as enzimas alfa glicosidase e alfa amilase, bem como o conteúdo de insulina no pâncreas. Camundongos diabéticos (STZ SAL e STZ EXT) e controles normoglicêmicos (CTL SAL e CTL EXT) foram tratados durante 21 dias com salina ou extrato bruto de M. bella na dose de 600 mg/kg. Foram coletados porções de fígado para avaliação da expressão de genes e proteínas envolvidos nos processos de glicogênese, glicogenólise e neoglicogênese. Ainda, amostras de músculo gastrocnêmio foram obtidas para avaliação de genes e proteínas envolvidas na via de sinalização de insulina e captação de glicose. Da mesma forma, a expressão das principais proteínas envolvidas na sinalização de insulina em tecido adiposo branco retroperitoneal também foi observada. O pâncreas foi coletado para avaliação do conteúdo de insulina. O tratamento com extrato bruto parece modular os processos de estoque e liberação de glicose no fígado de camundongos diabéticos (STZ EXT) através do aumento na expressão das proteínas glicogênio sintase e diminuição da expressão de PEPCK e glicose -6-fosfatase e dos respectivos genes responsáveis pela tradução das duas últimas. O tratamento com extrato de M. bella também promoveu aumento da expressão da proteína GLUT4 em tecido adiposo retroperitoneal de camundongos diabéticos (STZ EXT). Os ensaios in vitro e in vivo mostraram que o extrato é eficiente tanto na inibição das enzimas alfa glicosidase e alfa amilase assim como na diminuição da glicemia pós prandial, após ingestão de amido e maltose. Através dos resultados obtidos pudemos concluir, pelo menos em parte, que o extrato age na redução da glicemia de camundongos diabéticos através da modulação dos processos que regulam a captação, estoque e liberação de glicose pelo fígado. Ainda, sua ação também pode ser associada em parte pela captação de glicose pelo tecido adiposo, assim como pela inibição das enzimas alfa glicosidase e alfa amilase intestinais.
Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion or action, which results in carbohydrates, proteins and lipids metabolism disturbances. DM incidence increases alarmingly worldwide and studies with plants, which exhibit anti-diabetic effects, arouse researcher’s interests. In previous results we observed that streptozotocin-induced diabetic mice showed an improvement in diabetic condition after the treatment with Myrcia bella leaves crude extract. In this work, we have decided to evaluate the molecular mechanisms involved in glucose uptake and storage process in peripheral tissues such as liver, gastrocnemius muscle and adipose tissue. Furthermore, to evaluate the extract in vivo and in vitro inhibitory activity of alpha glycosidase and alpha amylase enzymes and insulin content in pancreas. Diabetic mice (STZ SAL and STZ EXT) and normoglicemic control mice (CTL SAL and CTL EXT) were treated during 21 days with saline or M. bella crude extract at 600 mg/kg. Liver was collected to gene and protein expression involved in glycogenesis, glycogenolysis and gluconeogenesis process. Gastrocnemius muscle to gene and protein expression involved in insulin signaling pathway and glucose uptake and white adipose tissue to the expression of the mainly proteins involved in insulin signaling pathway. Pancreas was collected to evaluate the insulin content. The treatment with M. bella crude extract seems to modulate the process of glucose storage and release in liver of diabetic mice (STZ EXT) thought the increase of glycogen synthase expression and decrease of the of PEPCK and glucose – 6- phosphatase expression as well as the respectively genes involved in the translation of PEPCK and glucose – 6- phosphatase . The treatment with M. bella extract also increased the GLUT4 protein expression in adipose tissue of diabetic mice (STZ EXT). The in vitro and in vivo analysis showed the extract is efficient in alpha glycosidase and amylase enzymes inhibition as well as in decreasing the postprandial glycemia after starch and maltose ingestion. Finally, we conclude that, at least in part, the extract acts in glycemia reduction through modulation of processes that regulates glucose uptake, storage and release from liver. Moreover, the extract action may be associated with the glucose uptake in adipose tissue as well as through the inhibition of alpha glycosidase and alpha amylase enzymes.
Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion or action, which results in carbohydrates, proteins and lipids metabolism disturbances. DM incidence increases alarmingly worldwide and studies with plants, which exhibit anti-diabetic effects, arouse researcher’s interests. In previous results we observed that streptozotocin-induced diabetic mice showed an improvement in diabetic condition after the treatment with Myrcia bella leaves crude extract. In this work, we have decided to evaluate the molecular mechanisms involved in glucose uptake and storage process in peripheral tissues such as liver, gastrocnemius muscle and adipose tissue. Furthermore, to evaluate the extract in vivo and in vitro inhibitory activity of alpha glycosidase and alpha amylase enzymes and insulin content in pancreas. Diabetic mice (STZ SAL and STZ EXT) and normoglicemic control mice (CTL SAL and CTL EXT) were treated during 21 days with saline or M. bella crude extract at 600 mg/kg. Liver was collected to gene and protein expression involved in glycogenesis, glycogenolysis and gluconeogenesis process. Gastrocnemius muscle to gene and protein expression involved in insulin signaling pathway and glucose uptake and white adipose tissue to the expression of the mainly proteins involved in insulin signaling pathway. Pancreas was collected to evaluate the insulin content. The treatment with M. bella crude extract seems to modulate the process of glucose storage and release in liver of diabetic mice (STZ EXT) thought the increase of glycogen synthase expression and decrease of the of PEPCK and glucose – 6- phosphatase expression as well as the respectively genes involved in the translation of PEPCK and glucose – 6- phosphatase . The treatment with M. bella extract also increased the GLUT4 protein expression in adipose tissue of diabetic mice (STZ EXT). The in vitro and in vivo analysis showed the extract is efficient in alpha glycosidase and amylase enzymes inhibition as well as in decreasing the postprandial glycemia after starch and maltose ingestion. Finally, we conclude that, at least in part, the extract acts in glycemia reduction through modulation of processes that regulates glucose uptake, storage and release from liver. Moreover, the extract action may be associated with the glucose uptake in adipose tissue as well as through the inhibition of alpha glycosidase and alpha amylase enzymes.
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Palavras-chave
Diabetes mellitus, metabolismo de glicose, Myrcia bella, fígado, tecido adiposo, adipose tissue, glucose metabolism, liver