title: Determinants of glomerular filtration and plasma flow in experimental diabetic rats.
abstract: GFR and, to a lesser extent, RPF are elevated soon after the onset of human diabetes mellitus. The mechanisms involved in these functional changes are unknown. Since the experimental diabetic rat has renal morphological changes similar to those observed in man, we investigated whole-kidney and superficial-nephron glomerular function in this animal model early during the course of the disease. Alloxan-induced diabetes (50 mg/kg BW) is frequently characterized by severe hyperglycemia and retarded body growth. Supplemental insulin administration (6 U of NPH insulin daily) results in normal body growth, although hyperglycemia persists. As a result, we studied four groups of diabetic rats (1) after 1 month of untreated diabetes, (2) after 3 months of untreated diabetes, (3) after 3 months of untreated diabetes followed by 1 month of insulin supplementation, and (4) after 3 months of insulin-supplemented diabetes. After 1 month of untreated diabetes, GFR and SNGFR each declined by 20% compared to age-matched control rats. RPF and SNGFR were both reduced by 33% as a consequence of a 41% increase in RT. Reduced SNGPF together with a 7 mm Hg reduction in PGC caused the fall in GFR and SNGFR. KWs were not significantly different from those of control rats. The functional changes that occurred after 1 month of untreated diabetes did not significantly deteriorate after 3 months of the disease. Insulin supplementation, when instituted for 1 month after 3 months of untreated diabetes, produced no significant improvement in either whole-kidney or superficial-nephron hemodynamics even though body and kidney growth were stimulated. In contrast, insulin supplementation initiated at the onset of diabetes increased both SNGFR and SNGFR to 23% above control values. GFR and RPF each increased in proportion to the 18% increment in kidney size. RT was reduced in these rats, and the pressures that govern glomerular ultrafiltration were not altered from control values. We conclude that in untreated diabetic rats, an increase in RT is the predominant hemodynamic alteration which produces reduced glomerular hemodynamic function. Once established, this defect may not be reversed with 1 month of insulin supplementation. In contrast, small doses of insulin initiated at the onset of diabetes result in renal hypertrophy and proportionate increases in GFR and RPF with a reduction in RT.
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D005455:Fluorescent Antibody Technique; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000098:blood supply*; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D012964:Sodium / Q000652:urine
chemical_list: D012964:Sodium; D011188:Potassium