Endocrine Abstracts (2006) 11 P251

The involvement of GH-IGF-I axis in a mouse model of type II diabetic nephropathy

Renana Eshet, Daniel Landau, Lital Wachsmann & Yael Segev

Ben Gurion University, Beer Sheva, Israel.

Type II diabetic nephropathy (DN) has become the single most common cause of end-stage renal disease in the Western world. In previous studies we have shown a significant involvement of the GH-IGF-I axis in a mouse model of type I DM. The purpose of this study was to examine the endocrine and renal changes in GH-IGF-I axis key molecules in db/db mice, a model of type II DM lacking a functional leptin receptor. Obese (D) and lean (heterozygote) (C) animals were followed, beginning at 6 weeks of age (at hyperglycemia onset), for a total of 4 weeks. Mean serum glucose levels in D animals during the study were 445±48 mg % vs 116±10 mg % in C. Serum GH levels at sacrifice were decreased in D (16±2 compared to 26±5 ng/ml in C; P<0.05). A similar decrease was seen for circulating IGF-I (237±7 vs 433±28 ng/ml in D vs C, P<0.05). Kidney weight was increased in D (169±3 vs 134±3 mg in C; P<0.05). In addition, hyperfiltration (214±18% of C), albuminuria (160±20% of C), glomerular hypertrophy (205±20%of C) and increased glomerular PAS deposition were observed in D animals. Renal IGFBP-1 protein was signifantly increased (241±39% of C) and renal IGF-I mRNA was decreased (70±7% of C) in D animals.

In conclusion, renal and glomerular hypertrophy, hyperfiltration, albuminuria and renal IGFBP-1 accumulation are seen in diabetic db/db mice already after 4 weeks of hyperglycemia, similar to finding in type I DM models. However, these renal changes are associated with low circulating IGF-I and GH levels, contrary to type I DM. This suggests that the renal complication in type II DM may be more affected by local diabetic environment.

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