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Volume 72, Issue 12, Pages 1512-1519 (December 2007)
Thiazolidinediones provide better renoprotection than insulin in an obese, hypertensive type II diabetic rat model S. Ohtomo, Y. Izuhara, S. Takizawa, N. Yamada, T. Kakuta, C. van Ypersele de Strihou, T. Miyata Kidney International Volume 72, Issue 12, Pages (December 2007) DOI: /sj.ki Copyright © 2007 International Society of Nephrology Terms and Conditions
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Figure 1 Metabolic abnormalities. (a) Body weight, (b) blood glucose, (c) insulin, (d) total cholesterol, (e) triglycerides, and (f) systolic blood pressure. SHR/NDmcr-cp rats were given vehicle (DM+V, closed square), PGZ (DM+PGZ, open square), were given insulin (DM+I, open triangle), and WKY rats on vehicle (WKY, closed triangle). Drug treatment was initiated at the age of 13 weeks after birth and lasted for 26 weeks. #P<0.05, ##P<0.01, ###P<0.001, WKY vs DM+V; *P<0.05, **P<0.01, ***P<0.001, DM+V vs DM+PGZ or DM+I; †P<0.05, ††P<0.01, †††P<0.001, DM+PGZ vs DM+I. Kidney International , DOI: ( /sj.ki ) Copyright © 2007 International Society of Nephrology Terms and Conditions
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Figure 2 Renal functions. (a) Urinary protein excretion and (b) creatinine clearance. SHR/NDmcr-cp rats were given vehicle (DM+V, closed square), PGZ (DM+PGZ, open square), were given insulin (DM+I, open triangle), and WKY rats on vehicle (WKY, closed triangle). PGZ significantly reduced urinary protein excretion throughout the whole period. By contrast, insulin reduced urinary total protein excretion only for the initial 8 weeks of treatment. Urinary protein excretion gradually increased thereafter and eventually there was no significant difference between SHD/NDmcr-cp on vehicle and on insulin. ###P<0.001, WKY vs DM+V; *P<0.05, **P<0.01, ***P<0.001, DM+V vs DM+PGZ or DM+I; †P<0.05, ††P<0.01, †††P<0.001, DM+PGZ vs DM+I. Kidney International , DOI: ( /sj.ki ) Copyright © 2007 International Society of Nephrology Terms and Conditions
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Figure 3 Glomerular sclerosis and tubulointerstitial fibrosis. (a–d) Periodic acid-Schiff-stained and (e–h) Masson trichrome-stained renal tissues. SHR/NDmcr-cp rats on (a and e) vehicle, (b and f) PGZ, or (c and g) insulin, and (d and h) WKY rats on vehicle at the end of the study. PGZ markedly improved glomerular sclerosis and tubulointerstitial fibrosis, whereas insulin failed to improve diabetic renal lesions. Original magnifications: (a–d) × 400 and (e–h) × 200. Kidney International , DOI: ( /sj.ki ) Copyright © 2007 International Society of Nephrology Terms and Conditions
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Figure 4 Advanced glycation and oxidative stress. (a) Renal pentosidine content, (b) gene expressions of Nox2 and (c) p47phox, and (d) correlation between renal pentosidine content and Nox2 expression. Both PGZ and insulin significantly decreased renal pentosidine and mRNA expressions of Nox2 and p47phox in diabetic kidneys. Pentosidine significantly correlated with Nox2 expression. ##P<0.01, ###P<0.001, WKY vs DM+V; *P<0.05, **P<0.01, ***P<0.001, DM+V vs DM+PGZ or DM+I. Kidney International , DOI: ( /sj.ki ) Copyright © 2007 International Society of Nephrology Terms and Conditions
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Figure 5 TGF-beta and insulin receptor in renal tissues. (a) TGF-β and (b) insulin receptor. PGZ, but not insulin, decreased mRNA expression of TGF-β significantly. Neither PGZ nor insulin influenced insulin receptor expression in diabetic kidney. ##P<0.01, WKY vs DM+V; **P<0.01, ***P<0.001, DM+V vs DM+PGZ or DM+I; †P<0.05, DM+PGZ vs DM+I. Kidney International , DOI: ( /sj.ki ) Copyright © 2007 International Society of Nephrology Terms and Conditions
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Figure 6 Induction of TGF-beta in vitro. (a) mRNA and (b) protein expressions in cultured rat proximal tubular cells (IRPTC). Insulin significantly enhanced TGF-β mRNA and protein expressions dose-dependently. *P<0.05, ***P<0.001. Kidney International , DOI: ( /sj.ki ) Copyright © 2007 International Society of Nephrology Terms and Conditions
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