We have previously reported that intrarenal angiotensin II (Ang II) levels are increased long before diabetes becomes apparent in obese Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a model of type 2 diabetes. In this study, we examined the changes in intrarenal renin-angiotensin system (RAS) activity in the developing kidneys of OLETF rats. Ang II contents and mRNA levels of RAS components were measured in male OLETF and control Long-Evans Tokushima (LETO) rats at postnatal days (PND) 1, 5, and 15, and at 4-30 weeks of age. In both LETO and OLETF rats, kidney Ang II levels peaked at PND 1, then decreased during the pre- and post-weaning periods. However, Ang II levels and gene expression of RAS components, including angiotensinogen (AGT), renin, and angiotensin-converting enzyme (ACE), were not significantly different between LETO and OLETF rats. Intrarenal Ang II contents further decreased during puberty (from 7 to 11 weeks of age) in LETO rats, bur not in OLETF rats. At 11 weeks of age, kidney Ang II levels, urinary AGT excretion, and mRNA levels of AGT and renin were higher in OLETF rats than in LETO rats, while blood glucose levels were not significantly different between these groups of rats. These data indicate that continued intrarenal expression of Ang II during pubescence contributes to the increases in intrarenal Ang II levels in prediabetic OLETF rats, and is associated with increased intrarenal AGT and renin expression. Inappropriate activation of the intrarenal RAS in the prediabetic stage may facilitate the onset and development of diabetic nephropathy in later life.
基金:
Ministry of Education, Culture, Sports, Science and Technology of JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [20590253]; Nation Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81141040]; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01DK072408] Funding Source: NIH RePORTER
第一作者单位:[1]Capital Med Univ, Beijing Tongren Hosp, Dept Tradit Chinese Med, Beijing 100730, Peoples R China[2]Kagawa Univ, Sch Med, Dept Pharmacol, Takamatsu, Kagawa 760, Japan[*1]Capital Med Univ, Beijing Tongren Hosp, Dept Tradit Chinese Med, Beijing 1,Dong Jiao Min Xiang St, Beijing 100730, Peoples R China
通讯作者:
通讯机构:[1]Capital Med Univ, Beijing Tongren Hosp, Dept Tradit Chinese Med, Beijing 100730, Peoples R China[2]Kagawa Univ, Sch Med, Dept Pharmacol, Takamatsu, Kagawa 760, Japan[*1]Capital Med Univ, Beijing Tongren Hosp, Dept Tradit Chinese Med, Beijing 1,Dong Jiao Min Xiang St, Beijing 100730, Peoples R China
推荐引用方式(GB/T 7714):
Fan Y. -Y.,Kobori H.,Nakano D.,et al.Aberrant Activation of the Intrarenal Renin-Angiotensin System in the Developing Kidneys of Type 2 Diabetic Rats[J].HORMONE and METABOLIC RESEARCH.2013,45(5):338-343.doi:10.1055/s-0032-1331256.
APA:
Fan, Y. -Y.,Kobori, H.,Nakano, D.,Hitomi, H.,Mori, H....&Nishiyama, A..(2013).Aberrant Activation of the Intrarenal Renin-Angiotensin System in the Developing Kidneys of Type 2 Diabetic Rats.HORMONE and METABOLIC RESEARCH,45,(5)
MLA:
Fan, Y. -Y.,et al."Aberrant Activation of the Intrarenal Renin-Angiotensin System in the Developing Kidneys of Type 2 Diabetic Rats".HORMONE and METABOLIC RESEARCH 45..5(2013):338-343