A novel somatostatin analogue prevents early renal complications in the nonobese diabetic mouse
| Autor: | Daniel Landau, Andrey Podshyvalov, Yael Segev, Leonid Katchko, Michel Afargan, Aviva Silbergeld, Moshe Phillip |
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| Rok vydání: | 2001 |
| Předmět: |
Blood Glucose
medicine.medical_specialty Renal glomerulus Kidney Glomerulus Renal function Nephropathy Diabetic nephropathy Mice Mice Inbred NOD Internal medicine Diabetes mellitus Insulin Secretion Albuminuria Animals Insulin Medicine insulin-like growth factor-I Diabetic Nephropathies RNA Messenger Insulin-Like Growth Factor I renal hypertrophy NOD mice diabetes business.industry Hypertrophy Organ Size Blotting Northern medicine.disease Insulin-Like Growth Factor Binding Protein 1 Diabetes Mellitus Type 1 Endocrinology Somatostatin Nephrology Creatinine Growth Hormone PTR-3173 Female medicine.symptom business |
| Zdroj: | Kidney International. 60:505-512 |
| ISSN: | 0085-2538 |
| Popis: | A novel somatostatin analogue prevents early renal complications in the nonobese diabetic mouse . Background PTR-3173 (S) is a novel somatostatin analogue that has been found to exert a prolonged inhibitory action on the growth hormone (GH)-insulin-like growth factor (IGF)-I axis, but not on insulin secretion. We investigated the potential effect of this agent on the development of markers of diabetic nephropathy in the nonobese diabetic (NOD) mouse model of insulin-dependent diabetes. Methods Female diabetic NOD mice treated with PTR-3173 (DS group) or saline (D) and their control groups of nonhyperglycemic age-matched littermates (C) and C mice treated with PTR-3173 (CS) were sacrificed three weeks after onset of diabetes. Results Serum GH was elevated in the D group, decreased in the DS group, and unchanged in the CS group. Serum IGF-I was significantly decreased in both the D and DS groups. Kidney weight, glomerular volume, albuminuria, and creatinine clearance were increased in the D animals and showed a trend toward normalization in the DS animals. Renal extractable IGF-I protein and IGFBP1 mRNA were increased in the D group and normalized in the DS group. Conclusions GH antagonism by PTR-3173 has a blunting effect on renal/glomerular hypertrophy, albuminuria, and glomerular filtration rate (GFR) in diabetic NOD mice. This phenomenon is apparently associated with the prevention of renal IGF-I accumulation. Thus, modulation of GH effects may have beneficial therapeutic implications in diabetic nephropathy. |
| Databáze: | OpenAIRE |
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