C-peptide and captopril are equally effective in lowering glomerular hyperfiltration in diabetic rats

• Published in: Nephrology, dialysis, transplantation Vol. 19; no. 6; pp. 1385 - 1391
• Main Authors: Samnegård, Björn, Jacobson, Stefan H., Johansson, Bo-Lennart, Ekberg, Karin, Isaksson, Britta, Wahren, John, Sjöquist, Mats
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-06-2004
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Associated diseases and complications; Biological and medical sciences; C-peptide; C-Peptide - pharmacology; captopril; Captopril - pharmacology; Diabetes Mellitus, Experimental - physiopathology; Diabetes. Impaired glucose tolerance; diabetic nephropathy; Emergency and intensive care: renal failure. Dialysis management; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Glomerular Filtration Rate - drug effects; glomerular hyperfiltration; Glomerulonephritis; Intensive care medicine; Kidney Glomerulus - drug effects; Kidney Glomerulus - physiopathology; Kidney Glomerulus/drug effects/physiopathology; Male; Medical sciences; Medicin och hälsovetenskap; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Rats; Rats, Sprague-Dawley; Regional Blood Flow - drug effects; renal blood flow; Endocrinopathy; Rat; Hemodialysis; Extrarenal dialysis; Peptidyl-dipeptidase A; Kidney disease; Urinary system disease; Enzyme; Captopril; Diabetes mellitus; Rodentia; renal blood flow; Enzyme inhibitor; Blood flow; Peptidases; Vertebrata; Mammalia; Nephropathy; Animal; C-peptide; Renal failure; Hydrolases; Peptidyl-dipeptidases; Antihypertensive agent; glomerular hyperfiltration; ACE inhibitor; diabetic nephropathy; Experimental/physiopathology; Rats; Sprague-Dawley; Diabetes Mellitus
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfh163

Background. C-peptide has been shown to reduce glomerular hyperfiltration, glomerular hypertrophy and urinary albumin excretion in type 1 diabetes, but its effect has not been compared with that of an angiotensin-converting enzyme inhibitor (ACEI) in the early stage of renal involvement in diabetes. Methods. Glomerular filtration rate (GFR) was measured in terms of inulin clearance and renal blood flow, using ultrasound technique, in four groups of streptozotocin-induced diabetic rats before and after a 60 min infusion of C-peptide (D-Cp), captopril (D-ACEI), C-peptide and captopril (D-Cp–ACEI) or placebo (D-placebo). In addition, a non-diabetic control group was studied before and after captopril infusion (C-ACEI). Results. GFR was 37–51% higher in the diabetic groups than in the control animals. GFR decreased after treatment in the D-Cp, D-ACEI and D-Cp–ACEI groups, but did not change in the D-placebo group. Blood flow increased by 26–32% in the three groups receiving captopril and by 5% in the diabetic groups treated with C-peptide alone or placebo. The increase in blood flow in the three ACEI-treated groups was significantly greater than in the D-placebo group. Filtration fraction fell significantly in all groups, but only in the combined D-Cp–ACEI group did it fall significantly more than in the D-placebo group. Conclusions. C-peptide and captopril lower diabetes-induced glomerular hyperfiltration to a similar extent, but the influence of captopril on blood flow is greater than that of C-peptide, suggesting different mechanisms of action. No statistically significant additive effects of C-peptide and captopril were shown in this acute infusion study.