A NEW SCREENING METHOD FOR ANTIDIABETICS BASED ON THE INTRAVENOUS GLUCOSE TOLERANCE TEST IN RABBITS

Abstract

Effect of some antidiabetics on the blood sugar curve after intravenous injection of glucose was investigated with the rabbits pre-treated with priscoline. Since an action of priscoline was found to make the curve type exponential, configuration of glucose tolerance curve could be determined by two constants, e^-k and C in a formula y_t=ae^-kt+C (y, blood sugar level; t, time; a, initial blood sugar).
Influences of antidiabetics, insulin, tolbutamide (N-toluyl-sulfonyl-N'-butylurea), metformin (Dimethylbiguanide) and sodium mesoxalate injected intravenously, were as follows:
(1)Examinations after single administrationa) After administration of 0.05u./kg of regular insulin, e^-k and C became both smaller than those for control. They were influenced in the similar way by subcutaneous injection of 0.1u./kg. b) After injection of 100mg/kg of tolbutamide, C value decreased significantly without change in e-k value. c) 50mg/kg of metformin gave an increasing effect on both of the two constants.
(2) Examinations after repeated administrationsAfter the administrations of 100mg/kg of sodium mesoxalate during 5 or 10 days, e^-k became smaller but Clarger.
(3) There were not any changes in e^-k and I values at ter single administration of 100mg/kg of the mesoxalate, or after the repeated administrations of 0.05u./kg of insulin, 100mg/kg of tolbutamide or 31mg/kg of the mesoxalate.
Mechanism of these actions was briefly referred to, and a possibility was discussed to apply this glucose tolerance test to the pharmacological screening method for antidiabetics.