Obtención de un modelo múrido de diabetes inducida por estreptozotocina útil en la evaluación farmacodinámica de la insulina regular
DOI:
https://doi.org/10.17533/10.17533/udea.vitae.v24n2(2)a02Keywords:
Diabetes Inducida por Estreptozotocina, Estreptozotocina, Insulina, Modelos Animales de Enfermedad, FarmacologíaAbstract
ANTECEDENTES. Existen múltiples modelos animales de diabetes, pero todavía no se ha validado uno útil para determinar la farmacodinamia de medicamentos. OBJETIVOS. Usar el modelo de inducción de diabetes mediante estreptozotocina equilibrada en ratones no emparentados, para determinar de forma precisa y reproducible la farmacodinamia de insulina regular. MÉTODOS. En ratones machos no emparentados de aproximadamente 37 g, se inyectó una dosis intraperitoneal de 150 mg/kg de una solución equilibrada de estreptozotocina. La glucemia (mg/dL) se midió a los 0, 7, 9, 14, 16, 17 y 18 días post-inducción. Una vez los ratones alcanzaron glucemias >300 mg/dL, se determinó la eficacia hipoglucemiante de insulina regular en tres experimentos independientes. El rango de dosis fue 0,25 UI/kg a 4 UI/kg. Una ecuación de decaimiento exponencial de dos parámetros se ajustó a los datos. RESULTADOS. Al día 18, el modelo tuvo una efectividad del 80% para producir diabetes (glucemia 446 ± 59 mg/dL), con mortalidad de sólo 2%. El coeficiente de variación intra e interexperimento fue ≤13%. Los parámetros farmacodinámicos de insulina fueron indistinguibles después de tres experimentos (P=0,32). La magnitud del efecto máximo fue -374 ± 30,7 mg/dL y la dosis efectiva 50 fue 1,34 ± 0,2 UI/kg. CONCLUSIÓN. El modelo de diabetes inducida por estreptozotocina equilibrada permitió determinar de manera reproducible la farmacodinamia de la insulina regular.
Palabras clave: Diabetes Inducida por Estreptozotocina, Estreptozotocina, Insulina, Modelos Animales de Enfermedad, Farmacología.
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