EFFECT OF S-21663 (PMS812), AN IMIDAZOLINE DERIVATIVE, ON GLUCOSE-TOLERANCE AND INSULIN-SECRETION IN A RAT MODEL OF TYPE-II DIABETES

We have studied the activity of S-21663 (PMS 812), a new imidazoline d erivative, in a rat model of Type II diabetes obtained by i.v. injecti on of a low dose (35 mg/kg) of streptozotocin, using glucose tolerance tests. Glucose tolerance and insulin secretion were measured as the D elta G and the Delta I, i.e., the respective increase in glycemia and insulinemia over 30 min after the glucose load. The rate of glucose di sappearance was calculated as the K coefficient and the insulin respon se to glucose as the Delta I/Delta G. After i.p. injection of S-21663, Delta G (millimoles per liter per minute) was decreased (71.7 +/- 10. 1 vs. 112.6 +/- 15.1; P <.05), whereas K was increased (3.3 +/- 0.3 vs . 1.5 +/- 0.1; P <.05). Insulin secretion was also largely improved De lta I/Delta G: 90.9 +/- 22.2 vs. 18.3 +/- 2.6; P <.05). Oral administr ation of the product was almost as efficient as i.p. injection. Chroni c treatment (15 days) increased the efficiency. Insulin secretion meas ured in vitro at both 2.8 and 16.6 mM glucose was quadrupled by S-2166 3 (100 mu M). S-21663 binds neither to alpha-2 adrenoceptors nor to kn own imidazoline binding Sites. S-21663 can be considered as a potentia l hypoglycemic agent in Type II diabetes.