Ameliorative effect of polydatin on hyperglycemia and renal injury in streptozotocin-induced diabetic rats

Lijuan Wang; Liji Huang; Nan Li; Junjun Miao; Wei Liu; Jiangyi Yu

doi:10.14715/cmb/2019.65.7.10

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Vol. 65 No. 7: Issue 7

Issue Published : October 14, 2019

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Ameliorative effect of polydatin on hyperglycemia and renal injury in streptozotocin-induced diabetic rats

https://doi.org/10.14715/cmb/2019.65.7.10

Lijuan Wang

Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, 210000, People's Republic of China

Liji Huang

Nan Li

The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, 210023, People's Republic of China

Junjun Miao

Wei Liu

The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, 210023, People's Republic of China

Jiangyi Yu

Corresponding Author(s) : Jiangyi Yu

ysxyt1@163.com

Cellular and Molecular Biology, Vol. 65 No. 7: Issue 7
Article Published : September 30, 2019

Abstract

To investigate the effect of polydatin on glucose transporter, blood glucose homeostasis and renal injury in streptozotocin (STZ)-induced diabetic rats. The in vitro inhibitory effect of polydatin on sodium-glucose cotransporter-1 (SGLT1) and 2 (SGLT2) was determined using HEK293 cells. The inhibitory effect of polydatin on GLUT1 and GLUT4 was evaluated using 3T3-L1 adipocytes. Streptozotocin-induced diabetic rats were used for this study. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), urea nitrogen, serum creatinine and urinary protein were determined using biochemical analyzer. Histopathological examination was performed on renal tissue. Serum levels of interleukin 1Î² (IL-1Î²), tumor necrosis factor Î± (TNF-Î±), monocyte chemoattractant protein 1 (MCP-1) and C-reactive protein (CRP) were also determined. Polydatin significantly inhibited SGLT1/2 and exhibited high selectivity for both GLUT1 and GLUT4. It significantly and dose-dependently decreased hyperglycemia, enhanced urine glucose excretion in the diabetic rats. The polydatin treatment significantly ameliorated symptoms of DN such as polyuria, polydipsia and hyperphagia. The hypoglycemic effect of polydatin was maintained throughout the treatment period. In addition,the levels of IL-1Î², TNF-Î±, MCP-1 and CRP were significantly reduced in treated group. Treatment with polydatin significantly ameliorated most of the structural and morphological changes induced by STZ. Moreover, the levels of urinary protein, serum creatinine and urea nitrogen were significantly reduced after treatment with polydatin. As a potential dual inhibitor of SGLT1/2, polydatin has high selectivity for GLUT1 and GLUT4. Its long-term administration delays the development of DN, protects renal function and ameliorates renal tissue injury.

Keywords

Polydatin Diabetic nephropathy Inflammatory factors SGLT Streptozotocin.

Wang, L., Huang, L., Li, N., Miao, J., Liu, W., & Yu, J. (2019). Ameliorative effect of polydatin on hyperglycemia and renal injury in streptozotocin-induced diabetic rats. Cellular and Molecular Biology, 65(7), 55–59. https://doi.org/10.14715/cmb/2019.65.7.10

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References

Gao HX, Regier EE, Close KL. International Diabetes Federation World Diabetes Congress 2015. J Diabetes 2016; 8: 300-304.
Han SH, Susztak K. The hyperglycemic and hyperinsulinemic combo gives you diabetic kidney disease immediately. Focus on "Combined acute hyperglycemic and hyperinsulinemic clamp induced profibrotic and proinflammatory responses in the kidney". Am J Phys 2014; 306: 198-199.
Xue R, Gui D, Zheng L, Zhai R, Wang F, Wang N. Mechanistic Insight and Management of Diabetic Nephropathy: Recent Progress and Future Perspective. J Diabetes Res 2017; 2017: 1839809.
Wright EM. Renal Na+-glucose cotransporters. Am J Physiol-Renal 2001; 280: 10-18.
Jurczak MJ, Lee H-Y, Birkenfeld AL. SGLT2 deletion improves glucose homeostasis and preserves pancreatic Î²-cell function. Diabetes 2011; 60: 890-898.
Chao EC, Henry RR. SGLT2 inhibition”a novel strategy for diabetes treatment. Nat Rev Drug Discov 2010; 9: 551-559.
Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev 2011; 91: 733-794.
Martín MG, Turk E, Lostao MP, Kerner C, Wright EM. Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption. Nat Genet 1996; 12: 216-220.
Zambrowicz B, Freiman J, Brown PM. LX4211, a Dual SGLT1/SGLT2 Inhibitor, Improved Glycemic Control in Patients With Type 2 Diabetes in a Randomized, Placebo-Controlled Trial. Clin Pharm Ther 2012; 92: 158-169.
Breyer MD, Böttinger E, Brosius FC 3rd, Coffman TM, Harris RC, Heilig CW, et al. Mouse models of diabetic nephropathy. J Am Soc Nephrol 2005; 16: 27-45.
Calderhead DM, Kitagawa K, Tanner LI, Holman GD, Lienhard GE. Insulin regulation of the two glucose transporters in 3T3-L1 adipocytes. J Biol Chem 1990; 265: 13800-13808.
Papadopoulou-Marketou N, Chrousos GP, Kanaka-Gantenbein C. Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis. Diabetes Metab Res Rev 2017; 33: 2.
Wolf G. New insights into the pathophysiology of diabetic nephropathy: from haemodynamics to molecular pathology. Eur J Clin Invest 2015; 34: 785-796.
List JF, Whaley JM. Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans. Kidney Int 2011; 79: 20-27.
da Silva PN, da Conceicao RA, Maia RDC, de Castro Barbosa ML. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors: a new antidiabetic drug class. Medchemcomm 2018; 9: 1273-1281.
Li Z, Xu X, Deng L. Design, synthesis and biological evaluation of nitric oxide releasing derivatives of dapagliflozin as potential anti-diabetic and anti-thrombotic agents. Bioorgan Med Chem 2018; 26: 3947-3952.
Jesus AR, Vila-Vicosa D, Machuqueiro M, Marques AP, Dore TM, Rauter AP. Targeting Type 2 Diabetes with C-Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation. J Med Chem 2017; 60: 568-579.
Li Y, Shi Z, Chen L, Zheng S, Li S, Xu B, et al. Discovery of a Potent, Selective Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitor (HSK0935) for the Treatment of Type 2 Diabetes. J Med Chem 2017; 60: 4173-4184.
van den Meiracker AH, Baggen RG, Pauli S, Lindemans A, Vulto AG, Poldermans D, et al. Spironolactone in type 2 diabetic nephropathy: Effects on proteinuria, blood pressure and renal function. J Hypertens 2006; 24: 2285-2292.
Ola MS, Nawaz MI, Siddiquei MM, Al-Amro S, Abu El-Asrar AM. Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy. J Diabetes Complications 2015; 74: 145-147.

References

Gao HX, Regier EE, Close KL. International Diabetes Federation World Diabetes Congress 2015. J Diabetes 2016; 8: 300-304.

Han SH, Susztak K. The hyperglycemic and hyperinsulinemic combo gives you diabetic kidney disease immediately. Focus on "Combined acute hyperglycemic and hyperinsulinemic clamp induced profibrotic and proinflammatory responses in the kidney". Am J Phys 2014; 306: 198-199.

Xue R, Gui D, Zheng L, Zhai R, Wang F, Wang N. Mechanistic Insight and Management of Diabetic Nephropathy: Recent Progress and Future Perspective. J Diabetes Res 2017; 2017: 1839809.

Wright EM. Renal Na+-glucose cotransporters. Am J Physiol-Renal 2001; 280: 10-18.

Jurczak MJ, Lee H-Y, Birkenfeld AL. SGLT2 deletion improves glucose homeostasis and preserves pancreatic Î²-cell function. Diabetes 2011; 60: 890-898.

Chao EC, Henry RR. SGLT2 inhibition”a novel strategy for diabetes treatment. Nat Rev Drug Discov 2010; 9: 551-559.

Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev 2011; 91: 733-794.

Martín MG, Turk E, Lostao MP, Kerner C, Wright EM. Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption. Nat Genet 1996; 12: 216-220.

Zambrowicz B, Freiman J, Brown PM. LX4211, a Dual SGLT1/SGLT2 Inhibitor, Improved Glycemic Control in Patients With Type 2 Diabetes in a Randomized, Placebo-Controlled Trial. Clin Pharm Ther 2012; 92: 158-169.

Breyer MD, Böttinger E, Brosius FC 3rd, Coffman TM, Harris RC, Heilig CW, et al. Mouse models of diabetic nephropathy. J Am Soc Nephrol 2005; 16: 27-45.

Calderhead DM, Kitagawa K, Tanner LI, Holman GD, Lienhard GE. Insulin regulation of the two glucose transporters in 3T3-L1 adipocytes. J Biol Chem 1990; 265: 13800-13808.

Papadopoulou-Marketou N, Chrousos GP, Kanaka-Gantenbein C. Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis. Diabetes Metab Res Rev 2017; 33: 2.

Wolf G. New insights into the pathophysiology of diabetic nephropathy: from haemodynamics to molecular pathology. Eur J Clin Invest 2015; 34: 785-796.

List JF, Whaley JM. Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans. Kidney Int 2011; 79: 20-27.

da Silva PN, da Conceicao RA, Maia RDC, de Castro Barbosa ML. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors: a new antidiabetic drug class. Medchemcomm 2018; 9: 1273-1281.

Li Z, Xu X, Deng L. Design, synthesis and biological evaluation of nitric oxide releasing derivatives of dapagliflozin as potential anti-diabetic and anti-thrombotic agents. Bioorgan Med Chem 2018; 26: 3947-3952.

Jesus AR, Vila-Vicosa D, Machuqueiro M, Marques AP, Dore TM, Rauter AP. Targeting Type 2 Diabetes with C-Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation. J Med Chem 2017; 60: 568-579.

Li Y, Shi Z, Chen L, Zheng S, Li S, Xu B, et al. Discovery of a Potent, Selective Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitor (HSK0935) for the Treatment of Type 2 Diabetes. J Med Chem 2017; 60: 4173-4184.

van den Meiracker AH, Baggen RG, Pauli S, Lindemans A, Vulto AG, Poldermans D, et al. Spironolactone in type 2 diabetic nephropathy: Effects on proteinuria, blood pressure and renal function. J Hypertens 2006; 24: 2285-2292.

Ola MS, Nawaz MI, Siddiquei MM, Al-Amro S, Abu El-Asrar AM. Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy. J Diabetes Complications 2015; 74: 145-147.

Author biographies is not available.