BACKGROUND: The role of nitric oxide (NO) is controversial in diabetes nephropathy progression and the mechanisms remain unknown, especially in non-obese type 2 diabetes. To examine mechanisms of nephropathy progression in non-obese type 2 diabetes, we used spontaneously diabetic Torii (SDT) rats, a newly established model of non-obese type 2 diabetes. METHODS: Fourteen male Sprague-Dawley rats were used as a control (20 weeks, n = 6; 30 weeks, n = 8), and 20-week-old male SDT rats were divided into 2 groups: diabetic (DM, n = 8) and DM + insulin (n = 8) groups. Twenty- and 36-week-old rats were sacrificed, and blood, urine, and histomorphometric analyses, mRNA expression analysis of endothelial NO synthase (eNOS) and NADPH oxidase, and blood pressure measurement were performed. RESULTS: At 36 weeks, NO metabolites, and 8-hydroxydeoxyguanosine (8-OHdG) were significantly higher in the diabetic group than in the other 2 groups. Further renal studies showed increased glomerular volume and mesangial area, and intensified eNOS, 8-OHdG, and nitrotyrosine immunostaining in the diabetic group. Oxidative and nitrosative stress were positively associated with increased glomerular volume and mesangial area, which were mostly recovered by insulin therapy. CONCLUSIONS: NO and oxidative stress increased in SDT rats, suggesting that these play key roles in nephropathy progression in non-obese type 2 diabetes. 2010 S. Karger AG, Basel.
BACKGROUND: The role of nitric oxide (NO) is controversial in diabetes nephropathy progression and the mechanisms remain unknown, especially in non-obese type 2 diabetes. To examine mechanisms of nephropathy progression in non-obese type 2 diabetes, we used spontaneously diabetic Torii (SDT) rats, a newly established model of non-obese type 2 diabetes. METHODS: Fourteen male Sprague-Dawley rats were used as a control (20 weeks, n = 6; 30 weeks, n = 8), and 20-week-old male SDT rats were divided into 2 groups: diabetic (DM, n = 8) and DM + insulin (n = 8) groups. Twenty- and 36-week-old rats were sacrificed, and blood, urine, and histomorphometric analyses, mRNA expression analysis of endothelial NO synthase (eNOS) and NADPH oxidase, and blood pressure measurement were performed. RESULTS: At 36 weeks, NO metabolites, and 8-hydroxydeoxyguanosine (8-OHdG) were significantly higher in the diabetic group than in the other 2 groups. Further renal studies showed increased glomerular volume and mesangial area, and intensified eNOS, 8-OHdG, and nitrotyrosine immunostaining in the diabetic group. Oxidative and nitrosative stress were positively associated with increased glomerular volume and mesangial area, which were mostly recovered by insulin therapy. CONCLUSIONS: NO and oxidative stress increased in SDT rats, suggesting that these play key roles in nephropathy progression in non-obese type 2 diabetes. 2010 S. Karger AG, Basel.
Authors: Adam Whaley-Connell; Javad Habibi; Zachary Panfili; Melvin R Hayden; Sarika Bagree; Ravi Nistala; Safwan Hyder; Bennett Krueger; Vincent Demarco; Lakshmi Pulakat; Carlos M Ferrario; Alan Parrish; James R Sowers Journal: Am J Nephrol Date: 2011-06-29 Impact factor: 3.754
Authors: Javad Habibi; Melvin R Hayden; James R Sowers; Lakshmi Pulakat; Roger D Tilmon; Camila Manrique; Guido Lastra; Vincent G Demarco; Adam Whaley-Connell Journal: Endocrinology Date: 2010-12-22 Impact factor: 4.736
Authors: Adam Whaley-Connell; Javad Habibi; Ravi Nistala; Melvin R Hayden; Lakshmi Pulakat; Catherine Sinak; Bonnie Locher; Carlos M Ferrario; James R Sowers Journal: Regul Pept Date: 2012-03-29