RESUMO
Acarbose is widely used as α-glucosidase inhibitor in the treatment of type Ⅱ diabetes. Actinoplanes sp. is used for industrial production of acarbose. As a secondary metabolite, the biosynthesis of acarbose is quite complex. In addition to acarbose, a few acarbose structural analogs are also accumulated in the culture broth of Actinoplanes sp., which are hard to remove. Due to lack of systemic understanding of the biosynthesis and regulation mechanisms of acarbose and its structural analogs, it is difficult to eliminate or reduce the biosynthesis of the structural analogs. Recently, the advances in omics technologies and molecular biology have facilitated the investigations of biosynthesis and regulatory mechanisms of acarbose and its structural analogs in Actinoplanes sp.. The genes involved in the biosynthesis of acarbose and its structural analogs and their regulatory mechanism have been extensively explored by using bioinformatics analysis, genetic manipulation and enzymatic characterization, which is summarized in this review.
Assuntos
Humanos , Acarbose/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Técnicas GenéticasRESUMO
Desde o Diabetes Control and Complications Trial (DCCT), a terapia insulínica intensiva tem sido direcionada para alcançar valores de glicemia e hemoglobina glicada (HbA1c) tão próximos do normal quanto a segurança permita. Entretanto, a hiperglicemia (especialmente a hiperglicemia pós-prandial) e a hipoglicemia continuam a ser um problema no manejo do diabetes tipo 1. O objetivo de associar outras drogas à terapia insulínica é diminuir a glicemia pós-prandial. A terapia adjunta pode ser dividida em três grupos, conforme seu mecanismo de ação: 1. Aumento da ação da insulina (metformina e tiazolidinedionas); 2. Alteração da liberação de nutrientes no trato gastrintestinal (acarbose e amilina); 3. Outros modos de ação [pirenzepina, fator de crescimento insulina-símile (IGF-1) e peptídeo semelhante ao glucagon 1 (GLP-1). Muitos desses agentes mostraram, em estudos de curto prazo, diminuição de 0,5 por cento a 1 por cento na HbA1c, diminuir a hiperglicemia pós-prandial e as doses diárias de insulina.
Since Diabetes Control and Complications Trial (DCCT), intensive therapy has been directed at achieving glucose and glycosylated hemoglobin (HbA1c) values as close to normal as possible regarding safety issues. However, hyperglycemia (especially postprandial hyperglycemia) and hypoglicemia continue to be problematic in the management of type 1 diabetes. The objective of associating other drugs to insulin therapy is to achieve better metabolic control lowering postprandial blood glucose levels. Adjunctive therapies can be divided in four categories based on their mechanism of action: enhancement of insulin action (e.g. the biguanides and thiazolidinediones), alteration of gastrointestinal nutrient delivery (e.g. acarbose and amylin) and other targets of action (e.g. pirenzepine, insulin-like growth factor I and glucagon-like peptide-1). Many of these agents have been found to be effective in short-term studies with decreases in HbA1c of 0.5-1 percent, lowering postprandial blood glucose levels and decreasing daily insulin doses.