Jódar Esteban
Servicio de Endocrinología y Nutrición Clínica, Hospital Universitario Quirón Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid, España.
Med Clin (Barc). 2014 Sep;143 Suppl 2:12-7. doi: 10.1016/S0025-7753(14)70103-4. Epub 2014 Oct 15.
Glucagon-like peptide 1 (GLP-1) is secreted from enteroendocrine L-cells in response to oral nutrient intake and elicits glucose-stimulated insulin secretion while suppressing glucagon secretion. Moreover slows gastric emptying -reducing postprandial glycemic excursions-, reduces body weight, systolic blood pressure and has beneficial effects in the cardiovascular and central nervous systems. Since the 1990s, the efficacy of GLP-1 in reducing blood glucose levels in type 2 diabetes (DM2) was well known. However, GLP-1 should be administered by chronic subcutaneous infusion because of the rapid cleavage by the enzyme dipeptidyl peptidase 4 (DPP-4). Hence, DPP-4 inhibitors -which increase pseudo-physiologically endogenous GLP-1 levels- were developed. In addition, several GLP-1 receptor agonists have been designed to avoid DPP-4-breakdown and/or rapid renal elimination and, therefore, induce a pharmacologic effect in the GLP-1 receptor: short-acting, long-acting, and prolonged-acting GLP-1 analogs. Each class has different structural, pharmacodynamic and clinical properties and could be administered in different therapeutical regimens giving us the opportunity to individualize the therapy of DM2.
胰高血糖素样肽1(GLP-1)由肠内分泌L细胞分泌,以响应口服营养物质摄入,并在抑制胰高血糖素分泌的同时引发葡萄糖刺激的胰岛素分泌。此外,它还能减缓胃排空(减少餐后血糖波动)、减轻体重、降低收缩压,并对心血管和中枢神经系统产生有益影响。自20世纪90年代以来,GLP-1在降低2型糖尿病(DM2)血糖水平方面的疗效已为人所知。然而,由于其会被二肽基肽酶4(DPP-4)迅速裂解,GLP-1需要通过长期皮下输注给药。因此,开发了DPP-4抑制剂(可使内源性GLP-1水平假性生理性升高)。此外,还设计了几种GLP-1受体激动剂,以避免DPP-4降解和/或快速经肾清除,从而在GLP-1受体上产生药理作用:短效、长效和延长作用的GLP-1类似物。每一类都具有不同的结构、药效学和临床特性,并且可以采用不同的治疗方案给药,这使我们有机会对DM2治疗进行个体化。