Effect of acute & chronic imipramine treatment on glucose homeostasis.

ABSTRACT

Single dose of imipramine (IMI) produced significant (P less than 0.05) hyperglycemia in rabbits, the effect peaking at 1 h. The hyperglycemic response was less marked in rabbits which were chronically pretreated with IMI for 4 wk. Simultaneous administration of insulin, oral glucose or adrenaline with single doses of IMI resulted in an enhancement of usual hypoglycemic/hyperglycemic responses of these agents. However, when these drugs were administered in chronically IMI fed animals there was complete reversion of the enhancement. Daily administration of adrenaline for further 6 days with IMI feeding in the chronically IMI treated rabbits, led to enhancement in the hyperglycemic response to adrenaline (P less than 0.001). In contrast, similar administration of insulin resulted in reduced hypoglycemia. Further, glucose feeding with IMI plus adrenaline or insulin in these animals did not result in any significant alteration in blood glucose level (BGL), as compared to oral glucose plus single doses of adrenaline or insulin. GTT done on the day next to drug treatment in rabbits chronically pretreated with IMI and than with IMI plus insulin, produced an enhanced hyperglycemic response, as compared with the control group (P less than 0.01). These observations indicate that acute (but not chronic) treatment with IMI not only produces a rise in BGL per se but also enhances the response to other agents which affect glucose homeostasis.