The Effect of Insulin Treatment on Rac1 Expression in Diabetic Kidney

被引：6
作者：
Gumustekin, Mukaddes [1 ]
Micili, Serap Cilaker [2 ]
Arici, Mualla Aylin [1 ]
Karaman, Meral [3 ]
Guneli, Mehmet Ensari [3 ]
Tekmen, Isil [2 ]
机构：
[1] Dokuz Eylul Univ, Sch Med, Dept Pharmacol, Izmir, Turkey
[2] Dokuz Eylul Univ, Sch Med, Dept Histol & Embryol, Izmir, Turkey
[3] Dokuz Eylul Univ, Sch Med, Dept Lab Anim Sci, Izmir, Turkey
来源：
RENAL FAILURE | 2013年 / 35卷 / 03期
关键词：
apoptosis; caspase-3; diabetic nephropathy; insulin; Rac1; TUBULAR EPITHELIAL-CELLS; NADPH OXIDASE; OXIDATIVE STRESS; APOPTOSIS; MELATONIN; NEPHROPATHY; PROTECTS; GLUCOSE; GTPASE; DAMAGE;
D O I：
10.3109/0886022X.2013.764256
中图分类号：
R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];
学科分类号：
1002 ; 100201 ;
摘要：
This study was designed to evaluate the renoprotective effect of insulin on diabetic nephropathy through Rac1 inhibition. Twenty Wistar rats were divided into three groups: control (C), diabetic (D), and insulin-treated diabetic (D + I). Diabetes was induced by a single streptozotocin (STZ) injection (45 mg/kg i.p.) in adult male rats. Diabetic animals were treated subcutaneously with insulin (6 U/kg), or saline once a day for 8 weeks. Age-matched control rats received only saline. The kidney tissue samples were analyzed by immunohistochemical staining for Rac1 and cleaved caspase-3 expressions and using the TUNEL method for determining apoptotic cells. Diabetes increased the number of TUNEL (+) cells and cleaved caspase-3 and Rac1 expression levels in kidney. Administration of insulin for 8 weeks reduced Rac1 expression and ameliorated histopathological changes in kidney of STZ-induced diabetes model. These results may suggest that the renoprotective effect of insulin at least partly results from inhibition of Rac1 overexpression.
引用
收藏
页码：396 / 402
页数：7
相关论文
共 24 条
[1]   Effects of NADPH oxidase inhibitor in diabetic nephropathy [J].
Asaba, K ;
Tojo, A ;
Onozato, ML ;
Goto, A ;
Quinn, MT ;
Fujita, T ;
Wilcox, CS .
KIDNEY INTERNATIONAL, 2005, 67 (05) :1890-1898
[2]   Response to comment on: American Diabetes Association. Standards of medical care in diabetes-2011 (vol 34, pg e54, 2011) [J].
Wysham, C. H. ;
Kirkman, M. S. .
DIABETES CARE, 2011, 34 (08) :1887-1887
[3]   Pathogenesis of diabetic nephropathy [J].
Cao, Zemin ;
Cooper, Mark E. .
JOURNAL OF DIABETES INVESTIGATION, 2011, 2 (04) :243-247
[4]  
Choudhury D, 2010, DISCOV MED, V10, P406
[5]   Short-term melatonin treatment improved diabetic nephropathy but did not affect hemorheological changes in diabetic rats [J].
Gumustekin, M. ;
Tekmen, I. ;
Guneli, E. ;
Tugyan, K. ;
Topcu, A. ;
Ergonen, A. T. ;
Ozdemir, M. H. ;
Uysal, N. ;
Bediz, C. S. .
PHARMAZIE, 2007, 62 (09) :693-698
[6]   Effect of melatonin on testicular damage in streptozotocin-induced diabetes rats [J].
Guneli, E. ;
Tugyan, K. ;
Ozturk, H. ;
Gumustekin, M. ;
Cilaker, S. ;
Uysal, N. .
EUROPEAN SURGICAL RESEARCH, 2008, 40 (04) :354-360
[7]   Glucose loading induces DNA fragmentation in rat proximal tubular cells [J].
Ishii, N ;
Ogawa, Z ;
Suzuki, K ;
Numakami, K ;
Saruta, T ;
Itoh, H .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1996, 45 (11) :1348-1353
[8]   TNF-α/cycloheximide-induced apoptosis in intestinal epithelial cells requires Rac1-regulated reactive oxygen species [J].
Jin, Shi ;
Ray, Ramesh M. ;
Johnson, Leonard R. .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2008, 294 (04) :G928-G937
[9]   Insulin administered at reoxygenation exerts a cardioprotective effect in myocytes by a possible anti-apoptotic mechanism [J].
Jonassen, AK ;
Brar, BK ;
Mjos, OD ;
Sack, MN ;
Latchman, DS ;
Yellon, DM .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2000, 32 (05) :757-764
[10]   Increased glomerular cell (podocyte) apoptosis in rats with streptozotocin-induced diabetes mellitus: role in the development of diabetic glomerular disease [J].
Menini, S. ;
Iacobini, C. ;
Oddi, G. ;
Ricci, C. ;
Simonelli, P. ;
Fallucca, S. ;
Grattarola, M. ;
Pugliese, F. ;
Pesce, C. ;
Pugliese, G. .
DIABETOLOGIA, 2007, 50 (12) :2591-2599
123