Activation of renal signaling pathways in db/db mice with type 2 diabetes

被引:89
作者
Feliers, D
Duraisamy, S
Faulkner, JL
Duch, J
Lee, AV
Abboud, HE
Choudhury, GG
Kasinath, BS
机构
[1] Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA
[2] GRECC, S Texas Vet Hlth Care Syst, San Antonio, TX USA
关键词
diabetic nephropathy; insulin receptor; phosphotidylinositol; 3-kinase; MAP kinase; Akt; receptor signaling; renal cortex;
D O I
10.1046/j.1523-1755.2001.060002495.x
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
Background. Altered regulation of signaling pathways may contribute to the pathogenesis of renal disease. We examined renal cortical signaling pathways in type 2 diabetes. Methods. The status of renal cortical signaling pathways was examined in control and db/db mice with type 2 diabetes in the early phase of diabetic nephropathy associated with renal matrix expansion and albuminuria. Results. Tyrosine phosphorylation of renal cortical proteins was increased in diabetic mice. Renal cortical activities of phosphatidylinositol 3-kinase (PI 3-kinase) in antiphosphotyrosine immunoprecipitates. Akt (PKB), and ERK1/2-type mitogen-activated protein (MAP) kinase activities were significantly augmented sixfold (P < 0.01), twofold (P < 0.0003), and sevenfold (P < 0.001). respectively, in diabetic mice compared with controls. A part of the increased renal cortical PI 3-kinase activity was due to insulin receptor activation. as PI 3-kinase activity associated with beta chain of the insulin receptor was increased nearly fourfold(P < 0.0235). Additionally. the kinase activity of the immunoprecipitated insulin receptor P chain was augmented in the diabetic renal cortex, and tyrosine phosphorylation of the insulin receptor was increased. In the liver, activities of PI 3-kinase in the antiphosphotyrosine immunoprecipitates and Akt also were increased threefold (P < 0.05) and twofold (P < 0.0002), respectively. However, there was no change in the hepatic insulin receptor-associated PI 3-kinase activity. Additionally, the hepatic ERK1/2-type MAP kinase activity was inhibited by nearly 50% (P < 0.01). Conclusions. These studies demonstrate that a variety of receptor signaling pathways are activated in the renal cortex of mice with type 2 diabetes, and suggest a role for augmented insulin receptor activity in nephropathy of type 2 diabetes.
引用
收藏
页码:495 / 504
页数:10
相关论文
共 50 条
[41]   Fibroblast Growth Factor 21 Improves Insulin Resistance and Ameliorates Renal Injury in db/db Mice [J].
Kim, H. W. ;
Lee, J. E. ;
Cha, J. J. ;
Hyun, Y. Y. ;
Kim, J. E. ;
Lee, M. H. ;
Song, H. K. ;
Nam, D. H. ;
Han, J. Y. ;
Han, S. Y. ;
Han, K. H. ;
Kang, Y. S. ;
Cha, D. R. .
ENDOCRINOLOGY, 2013, 154 (09) :3366-3376
[42]   Loss of Farnesoid X receptor (FXR) accelerates dysregulated glucose and renal injury in db/db mice [J].
Qiu, Yuxiang ;
Kang, Ningsu ;
Wang, Xi ;
Yao, Yao ;
Cui, Jun ;
Zhang, Xiaoyan ;
Zheng, Lu .
PEERJ, 2023, 11
[43]   Melatonin Ameliorates Renal Fibrosis Through the Inhibition of NF-κB and TGF-β1/Smad3 Pathways in db/db Diabetic Mice [J].
Fan, Zhe ;
Qi, Xiangming ;
Yang, Wenwen ;
Xia, Lingling ;
Wu, Yonggui .
ARCHIVES OF MEDICAL RESEARCH, 2020, 51 (06) :524-534
[44]   Restoration of Defective L-type Ca2+ Current in Cardiac Myocytes of Type 2 Diabetic db/db Mice by Akt and PKC-ι [J].
Lu, Zhongju ;
Ballou, Lisa M. ;
Jiang, Ya-Ping ;
Cohen, Ira S. ;
Lin, Richard Z. .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2011, 58 (04) :439-445
[45]   Impact of sex on diabetic nephropathy and the renal transcriptome in UNx db/db C57BLKS mice [J].
Sembach, Frederikke E. ;
Fink, Lisbeth N. ;
Johansen, Thea ;
Boland, Brandon B. ;
Secher, Thomas ;
Thrane, Sebastian T. ;
Nielsen, Jens C. ;
Fosgerau, Keld ;
Vrang, Niels ;
Jelsing, Jacob ;
Pedersen, Tanja X. ;
Ostergaard, Mette V. .
PHYSIOLOGICAL REPORTS, 2019, 7 (24)
[46]   Celastrol, an NF-κB Inhibitor, Improves Insulin Resistance and Attenuates Renal Injury in db/db Mice [J].
Kim, Jung Eun ;
Lee, Mi Hwa ;
Nam, Deok Hwa ;
Song, Hye Kyoung ;
Kang, Young Sun ;
Lee, Ji Eun ;
Kim, Hyun Wook ;
Cha, Jin Joo ;
Hyun, Young Youl ;
Han, Sang Youb ;
Han, Kum Hyun ;
Han, Jee Young ;
Cha, Dae Ryong .
PLOS ONE, 2013, 8 (04)
[47]   Antidiabetic Effect of Artemether in Db/Db Mice Involves Regulation of AMPK and PI3K/Akt Pathways [J].
Bai, Xiaolin ;
Pei, Ruixia ;
Lei, Wen ;
Zhao, Meiyun ;
Zhang, Jialin ;
Tian, Lu ;
Shang, Junke .
FRONTIERS IN ENDOCRINOLOGY, 2020, 11
[48]   Marein ameliorates diabetic nephropathy by inhibiting renal sodium glucose transporter 2 and activating the AMPK signaling pathway in db/db mice and high glucose-treated HK-2 cells [J].
Guo, Yanli ;
Ran, Zheng ;
Zhang, Yongwei ;
Song, Zhipeng ;
Wang, Lifeng ;
Yao, Lan ;
Zhang, Minfang ;
Xin, Jialiang ;
Mao, Xinmin .
BIOMEDICINE & PHARMACOTHERAPY, 2020, 131
[49]   Antidiabetic Effect of Tibetan Medicine Tang-Kang-Fu-San in db/db Mice via Activation of PI3K/Akt and AMPK Pathways [J].
Duan, Bailu ;
Zhao, Zhongqiu ;
Liao, Weifang ;
Xiong, Hui ;
Liu, Sisi ;
Yin, Liang ;
Gao, Tiexiang ;
Mei, Zhinan .
FRONTIERS IN PHARMACOLOGY, 2017, 8
[50]   NFAT2 inhibitor ameliorates diabetic nephropathy and podocyte injury in db/db mice [J].
Zhang, Li ;
Li, Ruizhao ;
Shi, Wei ;
Liang, Xinling ;
Liu, Shuangxin ;
Ye, Zhiming ;
Yu, Chunping ;
Chen, Yuanhan ;
Zhang, Bin ;
Wang, Wenjian ;
Lai, Yuxiong ;
Ma, Jianchao ;
Li, Zhuo ;
Tan, Xiaofan .
BRITISH JOURNAL OF PHARMACOLOGY, 2013, 170 (02) :426-439