Información del artículo
El GLP-1 (glucagon-like peptide-1) es una hormona con carácter de incretina que contribuye al control de la homeostasis de la glucosa, y que por su acción insulinotrópica, insulinotrófica y también insulinomimética, se está considerando para el tratamiento de la diabetes mellitus tipo 2. In vitro, el GLP-1 tiene efectos anabólicos sobre el metabolismo hepático de la glucosa en la rata normal y diabética, y sobre el del músculo y la grasa de la rata y del hombre; en el tejido adiposo, el GLP-1 es, además, lipolítico y lipogénico. En estos 3 tejidos extrapancreáticos, el GLP-1 parece actuar a través de receptores específicos, distintos en estructura y/o vía de señalización del pancreático, sobre los que se ha propuesto un inositolfosfoglicano como posible segundo mensajero. Por otro lado, la respuesta secretora de la célula β al GLP-1, modulada en condiciones normales por la concentración extracelular de glucosa, está alterada en la diabetes tipo 2, debido, posiblemente, a la imposibilidad de la célula para reconocer a la hexosa; sin embargo, nutrientes no glucídicos, capaces de sortear los defectos específicos de reconocimiento de la célula β diabética hacia la glucosa, como son los ésteres de ácidos dicarboxílicos, potencian y/o prolongan su acción insulinotrópica. Además, el GLP-1 no sólo ejerce un papel regulador de la ingestión de alimentos, induciendo sensación de saciedad, sino que también parece tener acciones beneficiosas en síndromes de carácter neurodegenerativo central y periférico. En cualquier caso, el valor del papel potencial terapéutico del GLP-1 no solo en la diabetes sino también en la obesidad y en las enfermedades cardíacas y nerviosas, es un hecho que no se debe ignorar, cuyo mecanismo de acción concreto, no del todo conocido, requiere aclaración.
Palabras clave:
GLP-1
Incretina
Diabetes
Obesidad
Alzheimer
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that contributes to the control of glucose homeostasis. Because of its insulinotropic, insulinotrophic and insulinomimetic actions, it is being considered for the treatment of type 2 diabetes mellitus. In vitro, GLP-1 has anabolic effects on glucose metabolism in the liver of normal and diabetic rats and in rat and human skeletal muscle and fat; moreover, in fat tissue, GLP-1 is also lipolytic and lipogenic. In these three extrapancreatic tissues, GLP-1 seems to act through specific receptors, distinct in structure and/or signaling pathway from pancreatic one, for which an inositolphosphoglycan has been proposed as a possible second messenger. The secretory response of β cells to GLP-1, modulated in normal conditions by the extracellular glucose concentration, is altered in type 2 diabetes mellitus, possibly due to the inability of the cell to recognize the hexose; however, non-glucose nutrients able to bypass the specific hexose recognition defects of the diabetic β cell, such as dicarboxylic acid esters, potentiate and/or prolong the insulinotropic action of GLP-1. Moreover, GLP-1 not only plays a regulatory role in food intake, by inducing satiety, but also seems to have beneficial effects on central and peripheral neurodegenerative syndromes. The value of the potential therapeutic role of GLP-1, not only in diabetes but also in obesity and cardiac and central nervous system diseases, should not be ignored, and its mechanism of action, which is not clearly understood, requires elucidation.
Key words:
GLP-1
Incretin
Diabetes
Obesity
Alzheimer
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