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Glucose intestinal absorption: a promising target for metformin and dietary proteins
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Resumo(s)
A Diabetes Mellitus é uma condição patológica, caracterizada pela existência de hiperglicémia, resultante da produção inadequada de insulina, e/ou resistência dos tecidos a esta hormona e/ou aumento da gluconeogénese.
Esta é classificada segundo o mecanismo fisiopatológico subjacente, pelo que é crucial conhecer os mecanismos que regulam a homeostasia da glucose.
A Diabetes Mellitus tipo 2, manifesta-se preferencialmente em adultos, e a primeira abordagem terapêutica desta patologia passa pela alteração do estilo de vida, contudo, sempre que esta se verifique ineficiente, é crucial iniciar-se uma abordagem farmacológica, sendo a Metformina a primeira linha de tratamento.
Os objetivos gerais desta monografia passam por aprofundar os conhecimentos acerca dos mecanismos de ação deste fármaco, determinar o papel dos péptidos intestinais na homeostasia da glucose e identificar o potencial terapêutico de uma dieta rica em proteínas nesta patologia.
A pesquisa bibliográfica teve por base a pesquisa de artigos científicos nas bases de dados Pubmed e SciELO, tendo sido aplicados descritores científicos, critérios de inclusão e limitadores de pesquisa
Estudos contemplando o papel da Metformina, concluíram que esta fomenta a diminuição da gluconeogénese e glucogenólise hepática e também a sensibilização dos tecidos periféricos à insulina. Para além da sua atividade hepática, a Metformina atua também no intestino. Este fármaco é absorvido na superfície apical dos enterócitos intestinais, através de transportadores identificados em estudos recentes.
Recentemente, o papel de alguns péptidos intestinais na regulação da homeostasia da glucose, tem ganho interesse investigacional. Estudos reforçam o papel modulador de um transportador de péptidos específico, o PepT1, que através da deteção de proteínas no lúmen intestinal, regula os níveis de glucose sanguínea, podendo este constituir uma nova estratégia terapêutica para esta patologia.
Nos últimos anos, verificou-se um aumento da procura por dietas ricas em proteína, existindo um crescimento no número de estudos que se debruçam sobre a manutenção dos níveis de glucose, após uma refeição rica em proteínas.
Assim, existe ainda um leque muito vasto de mecanismos que podem ser alvo de investigação, com intuito de serem formuladas novas estratégias terapêuticas para a Diabetes Mellitus 2.
Diabetes Mellitus is a pathological condition, characterized by the existence of hyperglycemia resulting from deficient production of insulin, and/or resistance of tissues to this hormone and/or increased gluconeogenesis. It is classically classified in diverse categories, which have a different pathophysiology, being crucial to know the mechanisms that regulate glucose homeostasis. Type 2 Diabetes Mellitus, manifests itself preferentially in adults, since, and the primary therapeutic approach regarding this pathology consists in lifestyle changes, however, whenever these are inefficient, it is crucial to start a pharmacological approach. Metformin is the first line of pharmacological treatment for type 2 Diabetes Mellitus. The general objectives of this manuscript are to deepen the knowledge on the mechanisms of action of this drug, determine the role of intestinal peptides in glucose homeostasis and identify the therapeutic potential of a protein-rich diet in this pathology. The bibliographic research was based on scientific articles from Pubmed and SciELO databases, using scientific descriptors, inclusion criteria and research limitations. Studies focusing the role of Metformin, concluded that it promotes not only the reduction of hepatic gluconeogenesis and glucogenolysis, but also the sensitization of peripheral tissues. In addition to its hepatic activity, Metformin also acts at the Intestines. This drug is absorbed through the apical surface of the intestinal enterocytes, through transporters identified in recent studies. Recently, the role of some intestinal peptides in regulating glucose homeostasis has gained research interest. Studies reinforce the modulating role of a specific peptide transporter, PepT1, which, through the detection of proteins in the intestinal lumen, regulates blood glucose levels, constituting a possible new therapeutic target for this pathology. In recent years, there has been an increase of the demand for high-protein diets, as there is an increase in the number of studies that focus on the maintenance of glucose levels after a protein-rich meal. Therefore, there is still a very wide range of mechanisms that can be investigated, with the aim of formulating new pharmacological strategies for type 2 Diabetes Mellitus.
Diabetes Mellitus is a pathological condition, characterized by the existence of hyperglycemia resulting from deficient production of insulin, and/or resistance of tissues to this hormone and/or increased gluconeogenesis. It is classically classified in diverse categories, which have a different pathophysiology, being crucial to know the mechanisms that regulate glucose homeostasis. Type 2 Diabetes Mellitus, manifests itself preferentially in adults, since, and the primary therapeutic approach regarding this pathology consists in lifestyle changes, however, whenever these are inefficient, it is crucial to start a pharmacological approach. Metformin is the first line of pharmacological treatment for type 2 Diabetes Mellitus. The general objectives of this manuscript are to deepen the knowledge on the mechanisms of action of this drug, determine the role of intestinal peptides in glucose homeostasis and identify the therapeutic potential of a protein-rich diet in this pathology. The bibliographic research was based on scientific articles from Pubmed and SciELO databases, using scientific descriptors, inclusion criteria and research limitations. Studies focusing the role of Metformin, concluded that it promotes not only the reduction of hepatic gluconeogenesis and glucogenolysis, but also the sensitization of peripheral tissues. In addition to its hepatic activity, Metformin also acts at the Intestines. This drug is absorbed through the apical surface of the intestinal enterocytes, through transporters identified in recent studies. Recently, the role of some intestinal peptides in regulating glucose homeostasis has gained research interest. Studies reinforce the modulating role of a specific peptide transporter, PepT1, which, through the detection of proteins in the intestinal lumen, regulates blood glucose levels, constituting a possible new therapeutic target for this pathology. In recent years, there has been an increase of the demand for high-protein diets, as there is an increase in the number of studies that focus on the maintenance of glucose levels after a protein-rich meal. Therefore, there is still a very wide range of mechanisms that can be investigated, with the aim of formulating new pharmacological strategies for type 2 Diabetes Mellitus.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2020, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Diabetes mellitus tipo 2 Glucose Metformina Péptidos Dieta rica em proteínas/pobre em hidratos de carbono Mestrado integrado - 2020