A. Alachi et R. Greenwood, HUMAN INSULIN ABSORPTION FROM THE INTESTINE IN DIABETIC RATS, Drug development and industrial pharmacy, 20(14), 1994, pp. 2333-2339
The ability of human insulin to produce hypoglycemia in streptozocin-d
iabetic rats (average weight 500 g) was investigated. A simple solutio
n of human insulin (insulin in hypotonic buffer solution) was administ
ered intraduodenally. Rats received a dose of insulin of either 200 U/
kg, 400 U/kg, or 600 U/kg. The hypoglycemic response was most signific
ant when 600 U/kg solution of insulin was administered. The 200 U/kg d
ose was of two forms; one form was a solution of insulin with a concen
tration 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. C
arrier-insulin systems were also introduced intraduodenally in strepto
zocin-diabetic rats. The results indicate that the carrier systems wit
hout insulin had glucogenic effect. Despite this glucogenic effect, ca
rrier-insulin systems at 200 U/kg dose were as effective as that of 60
0 U/kg of insulin solution. We conclude that insulin absorption from t
he intestine can cause a significant hypoglycemic state if given in a
large enough dose, even without the presence of other absorption enhan
cers in the dosage form.