THE EFFECT OF HYPERGLYCEMIA ON GLOMERULAR FUNCTION IN OBESE ZUCKER RATS

Studies were carried out in two groups of obese male Zucker rats with hereditary insulin resistance. Group 1 rats were made hyperglycemic by reducing beta-cell reserve with streptozotocin. Group 2 rats served a s controls. Group 1 rats exhibited hyperglycemia (blood glucose concen tration, 263 +/- 14 mg/dl) whereas insulin levels remained greater tha n those observed in lean rats (plasma insulin concentrations: group 1, 508 +/- 89 mU/ml; lean rats, 91 +/- 23 mU/ml). In group 2 rats more m arked hyperinsulinemia (plasma insulin concentration, 1096 +/- 234 mU/ ml) maintained normoglycemia (blood glucose concentration, 75 +/- 4 mg /dl). Studies at 5 week showed that hyperglycemic group 1 rats exhibit ed increases in kidney weight (group 1, 2.78 +/- 0.11 gm; group 2, 2.1 6 +/- 0.07 gm; p < 0.05) and glomerular filtration rate (GFR) (group 1 , 1.83 +/- 0.08 ml/min; group 2, 1.55 +/- 0.10 ml/min; p < 0.05). Micr opuncture revealed that the increase in GFR in hyperglycemic rats was attributable to increases in the single-nephron plasma flow rate (grou p 1, 225 +/- 16 nl/min; group 2, 172 +/- 14 nl/min; p < 0.05) and the glomerular ultrafiltration coefficient (group 1, 2.49 +/- 0.17 nl/min/ mm Hg; group 2, 2.02 +/- 0.14 nl/min/mm Hg; p < 0.05), which were not accompanied by an increase in glomerular transcapillary hydraulic pres sure (group 1, 49 +/- 1 mm Hg; group 2, 48 +/- 1 mm Hg). Morphologic s tudies revealed that the increase in GFR in group 1 was associated wit h an increase in glomerular volume (group 1, 3.46 +/- 0.15 x 10(6) m(3 ); group 2, 2.99 +/- 0.14 x 10(6) m(3); p < 0.05). These results indic ate that development of hyperglycemia in the setting of insulin resist ance can cause glomerular hyperfiltration and hypertrophy without incr easing glomerular capillary pressure.