EFFECT OF AMLODIPINE,FOSINOPRIL AND ATENOLOL ON GLUCOSE METABOLISM AND MICROALBUMINURIA IN STZ DIABETIC RATS
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This study compares the effect of a calcium channel blocker (amlodipine), an ACE inhibitor (fosinopril) and a BI-blocker (atenolol) on blood glucose level, plasma insulin level, insulin sensitivity and 24 hours urinary albumin excretion in groups of rats made diabetic by a single intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). Five groups of rats were used in this work. The first group (control non-diabetic rats) was normoglycemic with blood glucose level 116.8 ± 9.4 mg/di and 24 hour(H) urinary albumin 8.2 ± 1.2 mg/24 H urine.The other four groups were made diabetic by a single dose of STZ. The second group (control nontreated diabetic rats) exhibited hyperglycemia 8 weeks after induction of diabetes with blood glucose level 354 ± 32.6 mg/ dl, plasma insulin level 10.1 ± 0.8 mill/nil and 24 11 urinary albumin 42.6 ± 3.2 mg/24 H urine. Results of this study revealed that amlodipine oral administration in a dose of 5 mg/kg for 8 weeks in the third group of STZ diabetic rats induced a significant reduction of blood, glucose level (234 ± 18.6 versus 354 ± 32.6 in control diabetic rats. Pc 0.05) and plasma insulin level (8.2 ± 0.6 mIll/m1 ver- 149 sus 10.1 t 0.8 mllEml in control diabetic rats, P<0.05). Amlodipine also caused significant reduction in 24 H urinary albumin (18.2 ± 1.2 mg versus 42.6 ± 3.2 mg in control diabetic rats,P4).05) and significant improvement in sensitivity to intraperitoneal bolus dose of insulin where it caused a significant reduction in blood glucose level at OS H,1 H and 6 H after insulin compared to control diabetic rats, P<0.05. The results of this study also revealed that administration of fosinopril in a dose of 5 mg/kg/day oral to the fourth group of STZ diabetic rats for 8 weeks induced a significant reduction in blood glucose level ,plasma insulin level, and 24 H urinary albumin excretion compared to control non-treated diabetic rats. Fosinopril, also produced a significant improvement in insulin sensitivity at 0.5 H,1 H and 6 H after insulin injection compared to control non-treated diabetic rats. In contrast, stenolol given orally in a dose of 10 mg/kg/day for 8 weeks to fifth group of diabetic rats did not induce a significant change in blood glucose level ,plasma insulin level & 24 H urinary albumin and even reduced insulin sensitivity compared to control non-treated diabetic rats. It could be concluded from these results that both amlodipine and fosinopril are better antihypertensives than atenolol in diabetic patients as they improved glucose tolerance and albuminuria in STZ diabetic rats.