Phosphatase and Tension Homolog Overexpression in Insulin Resistant Diabetic Adipose Tissue△

doi:10.1016/S1001-9294(14)60063-8

Chinese Medical Sciences Journal ›› 2014, Vol. 29 ›› Issue (3): 167-173.doi: 10.1016/S1001-9294(14)60063-8

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Phosphatase and Tension Homolog Overexpression in Insulin Resistant Diabetic Adipose Tissue^△

Jing-bo Zeng^{1, 2}, Yun Zhang¹, Qi Sun¹, Yu-xiu Li^{1, *}

¹Department of Endocrinology, Key Laboratory of Endocrinology of the Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; ²Department of Endocrinology, Fuxing Hospital Affiliated to Capital University of Medical Sciences, Beijing 100038, China

出版日期:2014-09-29 发布日期:2014-09-29
通讯作者: *Corresponding author Tel: 86-10-69155088, Fax: 86-10-69155088, E-mail: liyuxiu@medmail.com.cn E-mail:liyuxiu@medmail.com.cn

Phosphatase and Tension Homolog Overexpression in Insulin Resistant Diabetic Adipose Tissue

Jing-bo Zeng^{1, 2}, Yun Zhang¹, Qi Sun¹, Yu-xiu Li^{1, *}

¹Department of Endocrinology, Key Laboratory of Endocrinology of the Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; ²Department of Endocrinology, Fuxing Hospital Affiliated to Capital University of Medical Sciences, Beijing 100038, China

Published:2014-09-29 Online:2014-09-29
Contact: *Corresponding author Tel: 86-10-69155088, Fax: 86-10-69155088, E-mail: liyuxiu@medmail.com.cn E-mail:liyuxiu@medmail.com.cn

摘要/Abstract

摘要： Objective To investigate the expression of phosphatase and tension homolog (PTEN) in adipose tissue of KKAy diabetic mice, a mouse model of type 2 diabetes. Methods KKAy diabetic mice were fed with high fat diet for 4 weeks. After blood glucose met the criteria of diabetes (over 16.7 mmol/L), mice were randomly divided into 3 groups: a control group (without any treatment), a rosiglitazone group (treated with rosiglitazone 12.5 mg/kg?d once per day), and a metformin group (treated with metformin 3 g/kg?d twice daily). After 4 weeks, we then determined the expression of PTEN and phosphoserine 473-Akt (pS473-Akt) in the epididymal adipose tissue with Western blots. The mice in each group were further divided into the insulin (-) subgroup and insulin (+) subgroup, which were intraperitoneally injected with saline and insulin (5 mU/g body weight), respectively. Results The expression of PTEN was elevated in the epididymal adipose tissue obtained from KKAy diabetic mice compared with that from the C57BL/6J mice (P<0.001). In accordance with the enhanced expression of PTEN, the level of pS473-Akt stimulated by insulin was decreased in the adipose tissue of KKAy mice compared to the C57BL/6J mice (P<0.001). Treatment with the insulin-sensitizing agents, rosiglitazone and metformin did not inhibit the elevated expression of PTEN in adipose tissue of KKAy diabetic mice. Conclusion PTEN may play an important role in the development of insulin resistance in adipose tissue of type 2 diabetes mice model.

关键词: insulin resistance, phosphatase and tension homolog, adipose tissue

Abstract: Objective To investigate the expression of phosphatase and tension homolog (PTEN) in adipose tissue of KKAy diabetic mice, a mouse model of type 2 diabetes. Methods KKAy diabetic mice were fed with high fat diet for 4 weeks. After blood glucose met the criteria of diabetes (over 16.7 mmol/L), mice were randomly divided into 3 groups: a control group (without any treatment), a rosiglitazone group (treated with rosiglitazone 12.5 mg/kg?d once per day), and a metformin group (treated with metformin 3 g/kg?d twice daily). After 4 weeks, we then determined the expression of PTEN and phosphoserine 473-Akt (pS473-Akt) in the epididymal adipose tissue with Western blots. The mice in each group were further divided into the insulin (-) subgroup and insulin (+) subgroup, which were intraperitoneally injected with saline and insulin (5 mU/g body weight), respectively. Results The expression of PTEN was elevated in the epididymal adipose tissue obtained from KKAy diabetic mice compared with that from the C57BL/6J mice (P<0.001). In accordance with the enhanced expression of PTEN, the level of pS473-Akt stimulated by insulin was decreased in the adipose tissue of KKAy mice compared to the C57BL/6J mice (P<0.001). Treatment with the insulin-sensitizing agents, rosiglitazone and metformin did not inhibit the elevated expression of PTEN in adipose tissue of KKAy diabetic mice. Conclusion PTEN may play an important role in the development of insulin resistance in adipose tissue of type 2 diabetes mice model.

Key words: insulin resistance, phosphatase and tension homolog, adipose tissue

基金资助: △Supported by National Natural Science Foundation of China (81270878) and National Key Program of Clinical Science of China (WBYZ2011-873)

Jing-bo Zeng, Yun Zhang, Qi Sun, Yu-xiu Li. Phosphatase and Tension Homolog Overexpression in Insulin Resistant Diabetic Adipose Tissue[J].Chinese Medical Sciences Journal, 2014, 29(3): 167-173.

参考文献 23

1.	Z, Wang H, Lee IH, et al. PTEN inhibition improves muscle regeneration in mice fed a high-fat diet. Diabetes 2010; 59: 1312-20.
2.	A, Dey CS. PTEN, a widely known negative regulator of insulin/PI3K signaling, positively regulates neuronal insulin resistance. Mol Biol Cell 2012; 23: 3882-98.
3.	JH, Lee JY, Kang SB, et al. Dietary monounsaturated fatty acids but not saturated fatty acids preserve the insulin signaling pathway via IRS-1/PI3K in rat skeletal muscle. Lipids 2010; 45: 1109-16.
4.	S, Sakamoto K, Johnstone L, et al. How moderate changes in Akt T-loop phosphorylation impact on tumorigenesis and insulin resistance. Dis Model Mech 2011; 4: 95-103.
5.	K, Fry EA, Taneja P. Recent progress in mouse models for tumor suppressor genes and its implications in human cancer. Clin Med Insights Oncol 2013; 7: 103-22.
6.	M, Bourgoin L, Foti M. PTEN in liver diseases and cancer. World J Gastroenterol 2010; 16: 4627-33.
7.	P, Jain SK. Hydrogen sulfide and L-cysteine increase phosphatidylinositol 3, 4, 5-trisphosphate (PIP3) and glucose utilization by inhibiting phosphatase and tensin homolog (PTEN) protein and activating phosphoi- nositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/protein kinase Cζ/λ (PKCζ/λ) in 3T3l1 adipocytes. J Biol Chem 2011; 286: 39848-59.
8.	N, Yoshida H, Kitagishi Y, et al. PI3K/AKT/PTEN signaling as a molecular target in leukemia angiogenesis. Adv Hematol 2012; 2012: 843085.
9.	MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol 2012; 13: 283-96.
10	HY, Hu B, Hu XB, et al. MiRNA-21 reverses high glucose and high insulin induced insulin resistance in 3T3-L1 adipocytes through targeting phosphatase and tensin homologue. Exp Clin Endocrinol Diabetes 2012; 120: 553-9.
11	H, Katagiri H, Funaki M, et al. Regulation of phosphoi- nositide metabolism, Akt phosphorylation, and glucose transport by PTEN (phosphatase and tensin homolog deleted on chromosome 10) in 3T3-L1 adipocytes. Mol Endocrinol 2001; 15: 1411-22.
12	X, Powelka AM, Soriano NA, et al. PTEN, but not SHIP2, suppresses insulin signaling through the phosphatidylinositol 3-kinase/Akt pathway in 3T3-L1 adipocytes. J Biol Chem 2005; 280: 22523-9.
13	M, Wada T, Fukui K, et al. Impact of lipid phosphatases SHIP2 and PTEN on the time- and Akt-isoform-specific amelioration of TNF-alpha-induced insulin resistance in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab 2009; 296: E157-64.
14	SC, Zhao G, Chang B, et al. Effects of exercise on expression and phosphorylation of PI3K and PKB in insulin signaling in the skeletal muscles of type 2 diabetic rats. Nan Fang Yi Ke Da Xue Xue Bao 2010; 30: 1217-21.
15	GR, Stalin A, Balakrishna K, et al. Insulin sensitization via partial agonism of PPARγ and glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway by embelin in type 2 diabetic rats. Biochim Biophys Acta 2013; 1830: 2243- 55.
16	A, Serrano M. PTEN in cancer, metabolism, and aging. Trends Endocrinol Metab 2013; 24: 184-9.
17	YT, Tsao CJ, Liu IM, et al. Increase of PTEN gene expression in insulin resistance. Horm Metab Res 2004; 36: 662-6.
18	JB, Li YX, Sun Q, et al. Increased protein PTEN expression in live and muscle in insulin resistant diabetic KKAy mice. Basic Clin Med 2007; 27: 166-8.
19	M, Gondha C, Sutliff R, et al. GDNF rescues hyperglycemia-induced diabetic enteric neuropathy through activation of the PI3K/Akt pathway. J Clin Invest 2006; 116: 344-56.
20	D, Esberg LB, Fang CX, et al. High-fat diet-induced juvenile obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxity and apoptosis. J Hypertens 2006; 24: 549- 61.
21	Y, Bandyopadhyay G, Sajan MP. Rosiglitazone, insulin treatment, and fasting correct defective activation of protein kinase C-zeta/lambda by insulin in vastus lateralis muscles and adipocytes of dabetics rats. Endocrinology 2001; 142: 1595-605.
22	Y, Bandyopadhyay G, Sajan MP, et al. Thiazolidine- dione treatment enhances insulin effects on protein kinase C-zeta/lambda activation and glucose transport in adipocytes of nondiabetic and Goto-Kakizaki type II diabetic rats. J Biol Chem 2000; 275: 16690-6.
23	LQ, Chen XL, Wang Q, et al. Upregulation of PTEN involved in rosiglitazone-induced apoptosis in human hepatocellular carcinoma cells. Acta Pharmacol Sin 2007; 28: 879-87.

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