Grønbaek H, Nielsen B, Frystyk J, Flyvbjerg A, Orskov H
Institute of Experimental Clinical Research, University Hospital of Aarhus, Denmark.
Exp Nephrol. 1996 Sep-Oct;4(5):295-303.
Initial diabetic renal hypertrophy is preceded by a transient increase in kidney insulin-like growth factor I(IGF-I). In the present study streptozotocin-diabetic rats were treated with a new somatostatin analogue (lanreotide), insulin or placebo for 7 days and compared to non-diabetic control rats. Kidney IGF-I changes were examined in the renal cortex, medulla, and whole kidney homogenates. The renal cortex contained approximately 5.5 times more IGF-I than the renal medulla (p < 0.01); further, IGF-I increased transiently and more pronouncedly in the renal cortex compared to the medulla. Lanreotide treatment significantly inhibited diabetic renal and glomerular growth compared to placebo-treated diabetic rats. Further, lanreotide treatment was followed by a significantly lower medulla IGF-I by day 2, while lanreotide had no effect on cortex IGF-I accumulation. In conclusion, IGF-I accumulated transiently and was more pronounced in the real cortex compared to the renal medulla and, further, lanreotide prevented diabetic renal and glomerular growth bringing new evidence that intervention with somatostatin analogues may have a role in the prevention of experimental diabetic kidney disease.
糖尿病性肾肥大初期,肾脏胰岛素样生长因子I(IGF-I)会出现短暂升高。在本研究中,用一种新的生长抑素类似物(兰瑞肽)、胰岛素或安慰剂对链脲佐菌素诱导的糖尿病大鼠进行为期7天的治疗,并与非糖尿病对照大鼠进行比较。检测肾皮质、髓质和全肾匀浆中IGF-I的变化。肾皮质中的IGF-I含量约为肾髓质的5.5倍(p < 0.01);此外,与髓质相比,肾皮质中IGF-I的升高更为短暂且明显。与安慰剂治疗的糖尿病大鼠相比,兰瑞肽治疗显著抑制了糖尿病性肾脏和肾小球的生长。此外,到第2天时,兰瑞肽治疗后肾髓质IGF-I显著降低,而兰瑞肽对皮质IGF-I的积累没有影响。总之,IGF-I短暂积累,且与肾髓质相比,在肾皮质中更为明显,此外,兰瑞肽可预防糖尿病性肾脏和肾小球的生长,这为生长抑素类似物干预可能在预防实验性糖尿病肾病中发挥作用提供了新证据。