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ABSTRACT
Diabetic nephropathy is a common microvascular complication of diabetes mellitus. Elevated plasma atrial natriuretic factor levels have been suggested as being one of the factors that contribute to the risk of developing diabetic nephropathy by increasing the intraglomerular pressure. In this study the inhibitory effect of glibornuride on the plasma atrial natriuretic factor (ANF) secretion was investigated in 10 (5 male and 5 female) newly diagnosed non - insulin - dependent diabetic patients (36 - 63 years old) and in 10 (5 male and 5 female) age and sex matched healthy controls (35 - 63 years old). Basal urine samples were taken for urine Na+ and K+. After normalizing the glycemia by means of euglycemic clamp, blood samples were taken for basal ANF from both diabetics and controls. Following one hour intravenous 0.9% saline infusion, blood samples for ANF and urine samples for Na+ and K+ were taken again. 24 hours later euglycemic state was provided by clamp technique and 50 mg glibornuride was given orally to the patient group. 30 minutes later the sae procedure was performed before and after saline infusion. Mean ANF levels increased significantly following 0.9% saline infusion in both the control group (From 11.13±0.85 pg/ml to 20.18±2.48 pg/ml) (p<0.05) and the diabetic group (from15.05±2.32pg/ml to 28.89±4.72 pg/ml) (p<0.05). The rate of increase in diabetics was similar to the controls (p<0.05). Basal urine Na+ and K+ excretions in the diabetic group were not different from the control group (p>0.05). in both control and diabetic groups, following the 0.9% saline infusion, mean urine Na+ excretion (from 11.73±1.14 mEq/h to 33.63±2.73 mEq/h to 10.54±1.24 mEq/h to 44.99±7.47 mEq/h respectively) and mean urine K+ excretion (from 3.33±0.62 mEq/h to 10.51±1.61 mEq/h nd from 2.70±0.24 mEq/h to 12.40±1.69 mEq/h respectively) increased significantly (p<0.05). However, diabetic subjects did not give any response to saline loading after glibornuride and ANF levels stayed unchanged (from 15.99±2.26 pg/ml to 15.13±1.00 pg/ml) (p>0.05). Although ANF levels did not change after saline infusion, mean urine Na+excretion İncreased (47.78±18.18 mEq/h) (p<0.05) but K+ excretion stayed at the same level (3.34±0.32 mEq/h) (p>0.05) in the diabetic group. These results suggested to us that, glibornuride may have an inhibitory effect on the ANF secretion and may provide a nonkaliuric natriuretic response to the volume loading by blocking the renal ATP sensitive K+ channels. This inhibitory effect may help to revert or prevent the hyperfiltration that is seen in the early stages of diabetes, which is thought to be caused by the high ANF levels and leads to diabetic nephropathy.
Diabetic nephropathy is a common microvascular complication of diabetes mellitus. Elevated plasma atrial natriuretic factor levels have been suggested as being one of the factors that contribute to the risk of developing diabetic nephropathy by increasing the intraglomerular pressure. In this study the inhibitory effect of glibornuride on the plasma atrial natriuretic factor (ANF) secretion was investigated in 10 (5 male and 5 female) newly diagnosed non - insulin - dependent diabetic patients (36 - 63 years old) and in 10 (5 male and 5 female) age and sex matched healthy controls (35 - 63 years old). Basal urine samples were taken for urine Na+ and K+. After normalizing the glycemia by means of euglycemic clamp, blood samples were taken for basal ANF from both diabetics and controls. Following one hour intravenous 0.9% saline infusion, blood samples for ANF and urine samples for Na+ and K+ were taken again. 24 hours later euglycemic state was provided by clamp technique and 50 mg glibornuride was given orally to the patient group. 30 minutes later the sae procedure was performed before and after saline infusion. Mean ANF levels increased significantly following 0.9% saline infusion in both the control group (From 11.13±0.85 pg/ml to 20.18±2.48 pg/ml) (p<0.05) and the diabetic group (from15.05±2.32pg/ml to 28.89±4.72 pg/ml) (p<0.05). The rate of increase in diabetics was similar to the controls (p<0.05). Basal urine Na+ and K+ excretions in the diabetic group were not different from the control group (p>0.05). in both control and diabetic groups, following the 0.9% saline infusion, mean urine Na+ excretion (from 11.73±1.14 mEq/h to 33.63±2.73 mEq/h to 10.54±1.24 mEq/h to 44.99±7.47 mEq/h respectively) and mean urine K+ excretion (from 3.33±0.62 mEq/h to 10.51±1.61 mEq/h nd from 2.70±0.24 mEq/h to 12.40±1.69 mEq/h respectively) increased significantly (p<0.05). However, diabetic subjects did not give any response to saline loading after glibornuride and ANF levels stayed unchanged (from 15.99±2.26 pg/ml to 15.13±1.00 pg/ml) (p>0.05). Although ANF levels did not change after saline infusion, mean urine Na+excretion İncreased (47.78±18.18 mEq/h) (p<0.05) but K+ excretion stayed at the same level (3.34±0.32 mEq/h) (p>0.05) in the diabetic group. These results suggested to us that, glibornuride may have an inhibitory effect on the ANF secretion and may provide a nonkaliuric natriuretic response to the volume loading by blocking the renal ATP sensitive K+ channels. This inhibitory effect may help to revert or prevent the hyperfiltration that is seen in the early stages of diabetes, which is thought to be caused by the high ANF levels and leads to diabetic nephropathy.