Renal Hypertrophy and Hyperfunction in Experimental Diabetes

Abstract

Induction of experimental diabetes causes a rapid increase in renal size, accompanied by parallel increases in total kidney RNA and protein, demonstrable 48–72 h after injection of streptozotocin. Within four days of diabetes the total glomerular volume increases by 30%, while tubules, which constitute the greater part of the kidney, grow relatively more slowly. However, the renal growth is apparent before any measurable kidney hyperfiltration. The diabetic renal hypertrophy is preceded by a rise in renal tissue concentration of insulin-like growth factor I (IGFI), which reaches a peak 24–48 h after induction of diabetes. Strict insulin treatment abolishes both kidney IGF-I accumulation and kidney growth. Administration of a long-acting somatostatin analogue (Octreotide) has an equally inhibitory effect on kidney IGF-I and growth and this without affecting the metabolic control. This finding supports the hypothesis that IGF-I accumulation is a prerequisite for initial renal growth. Furthermore, the renal IGF-I concentration is linearly dependent on the prevailing blood glucose levels, as has been shown for renal growth. The mechanisms responsible for kidney IGF-I accumulation are discussed, including a presentation of results for kidney IGF-I receptor number and affinity, as well as renal IGF-I mRNA levels during initial diabetic hypertrophy. These results thus indicate that IGF-I may contribute to early kidney growth in experimental diabetes and it is noteworthy that six months treatment with Octreotide in diabetic rats reduces both long-term renal hypertrophy and urinary albumin excretion without altering the metabolic status or renal function, suggesting that growth factors may be involved in long-term renal changes as well.