Human Insulin Absorption from the Intestine in Diabetic Rats

Abstract

The ability of human insulin to produce hypoglycemia in streptozocin-diabetic rats (average weight 500 g) was investigated. A simple solution of human insulin (insulin in hypotonic buffer solution) was administered intraduodenally. Rats received a dose of insulin of either 200 U/kg, 400 U/kg, or 600 U/kg. The hypoglycemic response was most significant when 600 U/kg solution of insulin was administered. The 200 U/kg dose was of two forms; one form was a solution of insulin with a concentration of 25 U/ml, 4 ml, and the other was a solution of insulin with a concentration of 50 U/ml, 2 ml. The dose of 25 U/ml, 4 ml produced a more significant hypoglycemic response than that of 50 U/ml, 2 ml. Carrier-insulin systems were also introduced intraduodenally in streptozocin-diabetic rats. The results indicate that the carrier systems without insulin had glucogenic effect. Despite this glucogenic effect, carrier-insulin systems at 200 U/kg dose were as effective as that of 600 U/kg of insulin solution. We conclude that insulin absorption from the intestine can cause a significant hypoglycemic state if given in a large enough dose, even without the presence of other absorption enhancers in the dosage form.