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Effect of puerarin on pancreatic β-cell injury in type 2 diabetic rats |
CHEN Xiufang1, LEI Kangfu1, DONG Min2, ZHENG Qiaomin2 |
1.Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035; 2.Central Laboratory of Biology, Wenzhou Medical University, Wenzhou, 325035 |
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Cite this article: |
CHEN Xiufang,LEI Kangfu,DONG Min, et al. Effect of puerarin on pancreatic β-cell injury in type 2 diabetic rats[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2017, 47(12): 859-863.
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Abstract Objective: To study the effects of puerarin on diabetic pancreatic β-cell injury and to explore its possible mechanisms in type 2 diabetic rats. Methods: A type 2 diabetic rat model was established by the combination of a high-fat diet and a single low-dose streptozocin intraperitoneal injection. The animals were randomly divided into diabetic model group and puerarin (100 mg•kg-1, i.p.) treatment group, with other 8 normal rats as a control group. The rats were treated daily for 4 consecutive weeks, and the equal volume of vehicle (5% propanediol, i.p.) was given to the normal control and diabetic model group. The rats were sacrificed and fasting blood glucose, glycated hemoglobin (HbA1c) and serum insulin levels, as well as malondialdehyde (MDA) content, the activities of superoxide dismutase (SOD) and catalase (CAT) in pancreas were measured. The pancreatic telomere length was determined by real-time quantitative PCR. The protein levels of phosphorylated AMP-activated protein kinase (AMPK), sirtuin1 (SIRT1) and uncoupling protein 2 (UCP2) as well as apoptosis-related proteins, e.g. cleaved caspase-3/caspase-3, Bim, Bax and Bcl-2 in pancreas were assessed by Western blot. Results: The fasting blood glucose, HbA1c, and MDA contents as well as the protein expressions of UCP2, Bax, Bim and cleaved caspase-3/caspase-3 in pancreas of diabetic rats were significantly higher than those in normal controls (P<0.01, respectively). However, insulin level in serum, SOD and CAT activities, telomere length as well as the protein expressions of p-AMPK/AMPK, SIRT1 and Bcl-2 in pancreas of diabetic rats were significantly decreased as compared with those in normal animals (P<0.01, respectively). In contrast, in puerarin treatment group, the above changes were reversed, significant differences of those were found as compared with those in diabetic model group (P<0.01, respectively). Conclusion: Puerarin exerts preventive and remedial effects on the diabetic pancreatic β-cell, which is probably due to protecting telomere length and inhibiting β-cell apoptosis via alleviating oxidative damage, and decreasing UCP2 expression through enhancing SIRT1 activity as well.
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Received: 08 June 2017
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[1] YANG S H, DOU K F, SONG W J. Prevalence of diabetes among men and women in China[J]. N Engl J Med, 2010, 362(25): 2425-2426.
[2] UK Prospective Diabetes Study (Ukpds) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)[J]. Lancet, 1998, 352(9131): 854-865.
[3] BUTLER A E, JANSON J, BONNER-WEIR S, et al. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes[J]. Diabetes, 2003, 52(1): 102-110.
[4] 陈秀芳, 董敏, 雷康福, 等. 葛根素对高血糖模型大鼠降糖作用的机制研究[J]. 中国药学杂志, 2010(16): 1242-1246.
[5] 陈秀芳, 雷康福, 董敏, 等. 葛根素对糖尿病大鼠心肌损伤的影响[J]. 中国病理生理杂志, 2010(4): 650-655.
[6] ZHOU Y X, ZHANG H, PENG C. Puerarin: a review of pharmacological effects[J]. Phytother Res, 2014, 28(7): 961-975.
[7] 陈秀芳, 董敏, 雷康福, 等. 葛根素对糖尿病大鼠坐骨神经损伤的影响[J]. 温州医学院学报, 2010, 40(5): 441-444.
[8] CAWTHON R M. Telomere measurement by quantitative PCR[J]. Nucleic Acids Res, 2002, 30(10): e47.
[9] DREWS G, KRIPPEIT-DREWS P, DUFER M. Oxidative stress and beta-cell dysfunction[J]. Pflugers Arch, 2010, 460(4): 703-718.
[10] KRAUSS S, ZHANG C Y, SCORRANO L, et al. Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction[J]. J Clin Invest, 2003, 112(12): 1831-1842.
[11] ZHANG D, SHEN M, MIKITA A, et al. Targeting uncoupling protein-2 improves islet graft function[J]. Cell Transplant, 2011, 20(3): 421-429.
[12] TAMURA Y, TAKUBO K, AIDA J, et al. Telomere attrition and diabetes mellitus[J]. Geriatr Gerontol Int, 2016, 16 Suppl 1: 66-74.
[13] ZHAO J, MIAO K, WANG H, et al. Association between telomere length and type 2 diabetes mellitus: a meta-analy-sis[J]. PLoS One, 2013, 8(11): e79993.
[14] MAD, ZHU W, HU S, et al. Association between oxidative stress and telomere length in Type 1 and Type 2 diabetic pa-tients[J]. J Endocrinol Invest, 2013, 36(11): 1032-1037.
[15] LI P, TONG Y, YANG H, et al. Mitochondrial translocation of human telomerase reverse transcriptase in cord blood mononuclear cells of newborns with gestational diabetes mellitus mothers[J]. Diabetes Res Clin Pract, 2014, 103(2): 310-318.
[16] WANG X. The expanding role of mitochondria in apoptosis[J]. Genes Dev,2001,15(22):2922-2933.
[17] LI Z, SHANGGUAN Z, LIU Y, et al. Puerarin protects pancreatic beta-cell survival via PI3K/Akt signaling pathway[J]. J Mol Endocrinol,2014,53(1):71-79.
[18] YANG L, YAO D, YANG H, et al. Puerarin protects pancreatic beta-cells in obese diabetic mice via activation of GLP-1R signaling[J]. Mol Endocrinol, 2016, 30(3): 361-371.
[19] YU J, AUWERX J. The role of sirtuins in the control of metabolic homeostasis[J]. Ann N Y Acad Sci, 2009, 1173 Suppl 1: E10-E19.
[20] LUU L, DAI F F, PRENTICE K J, et al. The loss of Sirt1 in mouse pancreatic beta cells impairs insulin secretion by disrupting glucose sensing[J]. Diabetologia, 2013, 56(9): 2010-2020.
[21] CANTO C, GERHART-HINES Z, FEIGE J N, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity[J]. Nature, 2009, 458(7241): 1056-1060.
[22] BORDONE L, MOTTA M C, PICARD F, et al. Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells[J]. PLoS Biol, 2006, 4(2): e31.
[23] MOYNIHAN K A, GRIMM A A, PLUEGER M M, et al. Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice[J]. Cell Metab, 2005, 2(2): 105-117. |
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