Effects of interaction between gliclazide and some calcium channel blockers on serum glucose, insulin and cortisol levels in non-diabetic and diabetic albino rats

ABSTRACT

The present work was conducted to study the effects of some calcium channel blockers[nifedipine and verapamil] on fasting serum glucose, insulin and in alloxan diabetic rats. Also the interactions between these calcium channel blockers and the oral hypoglycaemic sulfonylurea [gliclazide] were studied following the same parameters. It was found that oral administration of verapamil 20 mgm/kgm/day or nifedipine 1 mg/kgm/day for 15 succes sive days produced a significant elevation of serum glucose level accompanied by a significant reduction of serum insulin level in non diabetic rats, meanwhile in diabetic rats although they had significant reduced serum insulin level they did not elevate serum glucose level. This is probably due to some potential hypoglycaemic effects of calcium channel blockers that are only working in diabetic rats e.g. reduction of intestinal glucose absorption in diabetic rats and/ or blockade of the effects of hyperglucagonaemia that often prevails in type ll diabetes mellitus. Gliclazide 18 mg/kgm/day for 15 successive days produced a highly significant reduction of serum glucose level, accompanied by significant elevation of serum insulin in both non diabetic and diabetic rats. Coadministration of either calcium channel blockers with gliclazide significantly reduced it's hyperinsulinaemic effect in both groups of rats, whereas the gliclazide hypoglycaemic effect was abolished in non diabetic rats but in diabetic rats it was not signigicantly affected. As regards serum cortisol level neither verapamil nor nifedipine could produce any significant changes. Gliclazide elevated serum cortisol in nondiabetic rats only, such an effect that was abolished by coadministration of verapamil of nifedipine. Therefore, until a further detailed clinical study is available, it may be justifiable to follow up blood glucose level in patients under calcium channel blockers therapy and care should be exercised in using these drugs in potentially diabetic individuals. As regards the use of calcium channel blockers in diabetic patients under treatment with oral sulfonylurea, although they did not seem to adversely affect the control of diabetic state inspite of their hypoinsulinaemic effect as the present animal study proved, yet further evaluation of such interaction in human is still needed