THE ACCUMULATION OF IGF-I IN KIDNEYS OF STREPTOZOTOCIN-DIABETIC ADULT-RATS IS NOT ASSOCIATED WITH ELEVATED PLASMA GH OR IGF-I LEVELS

Nephropathy is a major complication of diabetes mellitus and is associ ated with expansion of the mesangium and an increase in kidney size in both humans and rats. Interestingly, early kidney enlargement occurs only in postpubertal animals, and is preceded by a significant increas e in the levels of extractable renal IGF-I. This study examined the po ssibility that this difference is CH dependent, and that very early ch anges in plasma GH and/or ICF-I in the adult animal are associated wit h an early accumulation of renal IGF-I. Silastic jugular catheters wer e placed in adult (13-14 week) male Sprague-Dawley (S-D) rats for bloo d collection and drug injection. Serial blood samples were taken every 30 min in groups of saline control and streptozotocin (STZ) (50 mu g/ kg, IV) rats from 1-6 h, 9-15 h, and 24-30 h post-injection, and plasm a GH profiles were determined by RIA. Renal ICF-I content was assessed following acid extraction. Following STZ, there was an immediate, ste p-wise reduction in peak GH levels (saline controls, 54 +/- 7 ng/ml vs 30 +/- 5 (1-6 h); 23 +/- 10 (9-15 h); and 13 +/- 3 ng/ml (24-30 h pos t-STZ); P<0.05 for all STZ groups vs control). The same significant st ep-wise reduction was observed in the integrated area under the curve for GH. A separate group of rats were treated with a GH-releasing fact or antagonist (CRF-AN) for 5 days prior to STZ, to suppress pulsatile GH release, and reduce plasma IGF-I. Chronic CRF-AN administration red uced plasma IGF-l levels significantly to 63% of control values (P<0.0 1). However, despite the reduction in plasma IGF-I, renal IGF-I remain ed significantly elevated 24 h post-STZ compared with controls and not significantly different from animals treated with STZ alone (467 +/- 49 ng IGF-I/g KW in control saline vs 778 +/- 100 in saline/STZ and 70 5 +/- 87 ng ICF-I/g KW in chronic GRF-AN/STZ rats (P<0.05)). In conclu sion, following STZ administration in the adult rat, there is an immed iate reduction in CH levels, indicating the renal IGF-I accumulation o ccurs without initial increases in plasma GH levels. Furthermore, when plasma IGF-I levels in the adult are significantly reduced renal IGF- I content remains elevated. These data suggest that early diabetic ren al growth is not associated with elevated circulating GH levels, and t hat high basal plasma IGF-I levels are not necessary for IGF-I accumul ation.