DETERMINANTS OF GLOMERULAR-FILTRATION AND PLASMA-FLOW IN EXPERIMENTAL DIABETIC RATS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 98  (6) , 869-885
Abstract
GFR [glomerular filtration rate] and, to a lesser extent, RPF [renal plasma flow] 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, whole-kidney and superficial-nephron [SN] glomerular function were investigated in this animal model early during the course of the disease. Alloxan-induced diabetes (50 mg/kg body wt) is frequently characterized by severe hyperglycemia and retarded body growth. Supplemental insulin administration (6 U of neutral protamine Hagedorn insulin daily) results in normal body growth, although hyperglycemia persists. As a result, 4 groups of diabetic rats were studied, after 1 mo. of untreated diabetes, after 3 mo. of untreated diabetes, after 3 mo. of untreated diabetes followed by 1 mo. of insulin supplementation and after 3 mo. of insulin-supplemented diabetes. After 1 mo. of untreated diabetes, GFR and SNGFR each declined by 20% compared to age-matched control rats. RPF and SNGPF [superficial nephron plasma flow rate] were both reduced by 33% as a consequence of a 41% increase in RT [total arteriolar resistance]. Reduced SNGPF together with a 7 mm Hg reduction in the glomerular capillary hydraulic pressure caused the fall in GFR and SNGFR. Kidney weights were not significantly different from those of control rats. The functional changes that occurred after 1 mo. of untreated diabetes did not significantly deteriorate after 3 mo. of the disease. Insulin supplementation, when instituted for 1 mo. after 3 mo. of untreated diabetes, produced no significant improvement in either whole-kidney or SN hemodynamics even though body and kidney growth were stimulated. In contrast, insulin supplementation initiated at the onset of diabetes increased both SNGFR and SNGPF 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. 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 mo. 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.