Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, slows the progression of renal complications through the suppression of renal inflammation, endoplasmic reticulum stress and apoptosis in prediabetic rats

Diabetes, Obesity and Metabolism

Volumn 20, Issue 11, 2018, Pages 2617-2626

  Jaikumkao, Krit ^a   Pongchaidecha, Anchalee ^a   Chueakula, Nuttawud ^a   Thongnak, La ongdao ^a   Wanchai, Keerati ^a,b   Chatsudthipong, Varanuj ^c   Chattipakorn, Nipon ^a   Lungkaphin, Anusorn ^a,d  

^a Faculty of Medicine Chiang Mai University   (Thailand)

^b MAE FAH LUANG UNIVERSITY   (Thailand)

^c Mahidol University ^*  (Thailand)

^d CHIANG MAI UNIVERSITY   (Thailand)

Author keywords

apoptosis; dapagliflozin; ER stress; inflammation; prediabetic condition; renal complications

Indexed keywords

DAPAGLIFLOZIN; MALONALDEHYDE; METFORMIN; SODIUM GLUCOSE COTRANSPORTER 1; SODIUM GLUCOSE COTRANSPORTER 2; SUPEROXIDE DISMUTASE; TRIACYLGLYCEROL; 2-(3-(4-ETHOXYBENZYL)-4-CHLOROPHENYL)-6-HYDROXYMETHYLTETRAHYDRO-2H-PYRAN-3,4,5-TRIOL; BENZHYDRYL DERIVATIVE; GLUCOSIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BODY WEIGHT LOSS; CONTROLLED STUDY; DIET INDUCED OBESITY; DISEASE ASSOCIATION; DISEASE EXACERBATION; DRUG EFFICACY; ENDOPLASMIC RETICULUM STRESS; HYPERCHOLESTEROLEMIA; HYPERINSULINEMIA; IMPAIRED GLUCOSE TOLERANCE; INSULIN RESISTANCE; INTRA-ABDOMINAL FAT; KIDNEY DYSFUNCTION; KIDNEY FIBROSIS; KIDNEY TISSUE; LIPID STORAGE; MALE; NEPHRITIS; NONHUMAN; PROTEIN EXPRESSION; RAT; RENAL PROTECTION; WISTAR RAT; ANIMAL; COMPLICATION; DRUG EFFECT; INFLAMMATION; KIDNEY; KIDNEY DISEASE; METABOLISM; PATHOLOGY; PHARMACOLOGY;

ANIMALS; APOPTOSIS; BENZHYDRYL COMPOUNDS; DISEASE PROGRESSION; ENDOPLASMIC RETICULUM STRESS; GLUCOSIDES; INFLAMMATION; KIDNEY; KIDNEY DISEASES; MALE; PREDIABETIC STATE; RATS; RATS, WISTAR; SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS;

EID: 85050496336     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.13441     Document Type: Article

References (72)

1. Metascreen Writing C, Bonadonna R, Cucinotta D, Fedele D, Riccardi G, Tiengo A. The metabolic syndrome is a risk indicator of microvascular and macrovascular complications in diabetes: results from Metascreen, a multicenter diabetes clinic-based survey. Diabetes Care. 2006;29:2701-2707
2. Decleves AE, Mathew AV, Cunard R, Sharma K. AMPK mediates the initiation of kidney disease induced by a high-fat diet. J Am Soc Nephrol. 2011;22:1846-1855
3. Shevalye H, Lupachyk S, Watcho P, et al. Prediabetic nephropathy as an early consequence of the high-calorie/high-fat diet: relation to oxidative stress. Endocrinology. 2012;153:1152-1161
4. Wang D, Luo Y, Wang X, et al. The sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents renal and liver disease in western diet induced obesity mice. Int J Mol Sci. 2018;19:137
5. Chueakula N, Jaikumkao K, Arjinajarn P, et al. Diacerein alleviates kidney injury through attenuating inflammation and oxidative stress in obese insulin-resistant rats. Free Radic Biol Med. 2017;115:146-155
6. Romagnani P, Remuzzi G, Glassock R, et al. Chronic kidney disease. Nat Rev Dis Primers. 2017;3:17088
7. Park JH, Choi BH, Ku SK, et al. Amelioration of high fat diet-induced nephropathy by cilostazol and rosuvastatin. Arch Pharm Res. 2017;40:391-402
8. D'Agati VD, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis. 2004;43:368-382
9. Wanchai K, Yasom S, Tunapong W, et al. Prebiotic prevents impaired kidney and renal Oat3 functions in obese rats. J Endocrinol. 2018;237:29-42
10. Yang P, Xiao Y, Luo X, et al. Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice. J Lipid Res. 2017;58:1417-1427
11. Stewart T, Jung FF, Manning J, Vehaskari VM. Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension. Kidney Int. 2005;68:2180-2188
12. Rivero A, Mora C, Muros M, Garcia J, Herrera H, Navarro-Gonzalez JF. Pathogenic perspectives for the role of inflammation in diabetic nephropathy. Clin Sci (Lond). 2009;116:479-492
13. Vallon V, Thomson SC. Renal function in diabetic disease models: the tubular system in the pathophysiology of the diabetic kidney. Annu Rev Physiol. 2012;74:351-375
14. Morrisey K, Evans RA, Wakefield L, Phillips AO. Translational regulation of renal proximal tubular epithelial cell transforming growth factor-beta1 generation by insulin. Am J Pathol. 2001;159:1905-1915
15. Lupia E, Elliot SJ, Lenz O, et al. IGF-1 decreases collagen degradation in diabetic NOD mesangial cells: implications for diabetic nephropathy. Diabetes. 1999;48:1638-1644
16. Sureshbabu A, Muhsin SA, Choi ME. TGF-beta signaling in the kidney: profibrotic and protective effects. Am J Physiol Renal Physiol. 2016;310:F596-F606
17. Fu S, Yang L, Li P, et al. Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature. 2011;473:528-531
18. Zhuang A, Forbes JM. Stress in the kidney is the road to pERdition: is endoplasmic reticulum stress a pathogenic mediator of diabetic nephropathy? J Endocrinol. 2014;222:R97-R111
19. Yoneda T, Imaizumi K, Oono K, et al. Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem. 2001;276:13935-13940
20. Fang DL, Wan Y, Shen W, et al. Endoplasmic reticulum stress leads to lipid accumulation through upregulation of SREBP-1c in normal hepatic and hepatoma cells. Mol Cell Biochem. 2013;381:127-137
21. Marciniak SJ, Yun CY, Oyadomari S, et al. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 2004;18:3066-3077
22. Hitomi J, Katayama T, Eguchi Y, et al. Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell death. J Cell Biol. 2004;165:347-356
23. Jaikumkao K, Pongchaidecha A, Thongnak LO, et al. Amelioration of renal inflammation, endoplasmic reticulum stress and apoptosis underlies the protective effect of low dosage of atorvastatin in gentamicin-induced nephrotoxicity. PLoS One. 2016;11:e0164528
24. Wang C, Wu M, Arvapalli R, et al. Acetaminophen attenuates obesity-related renal injury through ER-mediated stress mechanisms. Cell Physiol Biochem. 2014;33:1139-1148
25. Li C, Lin Y, Luo R, et al. Intrarenal renin-angiotensin system mediates fatty acid-induced ER stress in the kidney. Am J Physiol Renal Physiol. 2016;310:F351-F363
26. Vallon V, Gerasimova M, Rose MA, et al. SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice. Am J Physiol Renal Physiol. 2014;306:F194-F204
27. Komala MG, Panchapakesan U, Pollock C, Mather A. Sodium glucose cotransporter 2 and the diabetic kidney. Curr Opin Nephrol Hypertens. 2013;22:113-119
28. Lambers Heerspink HJ, de Zeeuw D, Wie L, Leslie B, List J. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013;15:853-862
29. Ptaszynska A, Johnsson KM, Parikh SJ, de Bruin TW, Apanovitch AM, List JF. Safety profile of dapagliflozin for type 2 diabetes: pooled analysis of clinical studies for overall safety and rare events. Drug Saf. 2014;37:815-829
30. Jabbour SA, Hardy E, Sugg J, Parikh S, Study G. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Diabetes Care. 2014;37:740-750
31. Terami N, Ogawa D, Tachibana H, et al. Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice. PLoS One. 2014;9:e100777
32. Ishibashi Y, Matsui T, Yamagishi S. Tofogliflozin, A highly selective inhibitor of SGLT2 blocks Proinflammatory and Proapoptotic effects of glucose overload on proximal tubular cells partly by suppressing oxidative stress generation. Horm Metab Res. 2016;48:191-195
33. Kojima N, Williams JM, Takahashi T, Miyata N, Roman RJ. Effects of a new SGLT2 inhibitor, luseogliflozin, on diabetic nephropathy in T2DN rats. J Pharmacol Exp Ther. 2013;345:464-472
34. Kojima N, Williams JM, Slaughter TN, et al. Renoprotective effects of combined SGLT2 and ACE inhibitor therapy in diabetic Dahl S rats. Physiol Rep. 2015;3(7):pii:e12436
35. Gallo LA, Ward MS, Fotheringham AK, et al. Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice. Sci Rep. 2016;6:26428
36. Benzler J, Ganjam GK, Pretz D, et al. Central inhibition of IKKbeta/NF-kappaB signaling attenuates high-fat diet-induced obesity and glucose intolerance. Diabetes. 2015;64:2015-2027
37. Edeling M, Ragi G, Huang S, Pavenstadt H, Susztak K. Developmental signalling pathways in renal fibrosis: the roles of notch, Wnt and hedgehog. Nat Rev Nephrol. 2016;12:426-439
38. D'Agati VD, Kaskel FJ, Falk RJ. Focal segmental glomerulosclerosis. N Engl J Med. 2011;365:2398-2411
39. Mahfoudh-Boussaid A, Zaouali MA, Hauet T, et al. Attenuation of endoplasmic reticulum stress and mitochondrial injury in kidney with ischemic postconditioning application and trimetazidine treatment. J Biomed Sci. 2012;19:71
40. Chen J, Guo Y, Zeng W, et al. ER stress triggers MCP-1 expression through SET7/9-induced histone methylation in the kidneys of db/db mice. Am J Physiol Renal Physiol. 2014;306:F916-F925
41. Lakshmanan AP, Thandavarayan RA, Palaniyandi SS, et al. Modulation of AT-1R/CHOP-JNK-Caspase12 pathway by olmesartan treatment attenuates ER stress-induced renal apoptosis in streptozotocin-induced diabetic mice. Eur J Pharm Sci. 2011;44:627-634
42. Albertoni Borghese MF, Majowicz MP, Ortiz MC, Passalacqua Mdel R, Sterin Speziale NB, Vidal NA. Expression and activity of SGLT2 in diabetes induced by streptozotocin: relationship with the lipid environment. Nephron Physiol. 2009;112:p45-p52
43. Vallon V, Rose M, Gerasimova M, et al. Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus. Am J Physiol Renal Physiol. 2013;304:F156-F167
44. Ojima A, Matsui T, Nishino Y, Nakamura N, Yamagishi S. Empagliflozin, an inhibitor of sodium-glucose Cotransporter 2 exerts anti-inflammatory and Antifibrotic effects on experimental diabetic nephropathy partly by suppressing AGEs-receptor Axis. Horm Metab Res. 2015;47:686-692
45. Nakamura N, Matsui T, Ishibashi Y, Yamagishi S. Insulin stimulates SGLT2-mediated tubular glucose absorption via oxidative stress generation. Diabetol Metab Syndr. 2015;7:48
46. Imprialos KP, Stavropoulos K, Doumas M, Karagiannis A, Athyros VG. The effect of SGLT2 inhibitors on cardiovascular events and renal function. Expert Rev Clin Pharmacol. 2017;10:1251-1261
47. Jia Y, He J, Wang L, et al. Dapagliflozin aggravates renal injury via promoting gluconeogenesis in db/db mice. Cell Physiol Biochem. 2018;45:1747-1758
48. Bonner C, Kerr-Conte J, Gmyr V, et al. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med. 2015;21:512-517
49. Novikov A, Vallon V. Sodium glucose cotransporter 2 inhibition in the diabetic kidney: an update. Curr Opin Nephrol Hypertens. 2016;25:50-58
50. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128
51. Sattar N, McLaren J, Kristensen SL, Preiss D, McMurray JJ. SGLT2 inhibition and cardiovascular events: why did EMPA-REG outcomes surprise and what were the likely mechanisms? Diabetologia. 2016;59:1333-1339
52. Jiang T, Wang Z, Proctor G, et al. Diet-induced obesity in C57BL/6J mice causes increased renal lipid accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1c-dependent pathway. J Biol Chem. 2005;280:32317-32325
53. Kume S, Uzu T, Araki S, et al. Role of altered renal lipid metabolism in the development of renal injury induced by a high-fat diet. J Am Soc Nephrol. 2007;18:2715-2723
54. Jauregui A, Mintz DH, Mundel P, Fornoni A. Role of altered insulin signaling pathways in the pathogenesis of podocyte malfunction and microalbuminuria. Curr Opin Nephrol Hypertens. 2009;18:539-545
55. Leamy AK, Egnatchik RA, Young JD. Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease. Prog Lipid Res. 2013;52:165-174
56. Ozcan U, Cao Q, Yilmaz E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004;306:457-461
57. Unger RH. Longevity, lipotoxicity and leptin: the adipocyte defense against feasting and famine. Biochimie. 2005;87:57-64
58. Dominguez J, Wu P, Packer CS, Temm C, Kelly KJ. Lipotoxic and inflammatory phenotypes in rats with uncontrolled metabolic syndrome and nephropathy. Am J Physiol Renal Physiol. 2007;293:F670-F679
59. Tabas I, Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol. 2011;13:184-190
60. Sarafidis PA, Ruilope LM. Insulin resistance, hyperinsulinemia, and renal injury: mechanisms and implications. Am J Nephrol. 2006;26:232-244
61. Tang L, Wu Y, Tian M, et al. Dapagliflozin slows the progression of the renal and liver fibrosis associated with type 2 diabetes. Am J Physiol Endocrinol Metab. 2017;313:E563-E576
62. Anderson SL. Dapagliflozin efficacy and safety: a perspective review. Ther Adv Drug Saf. 2014;5:242-254
63. Panchapakesan U, Pegg K, Gross S, et al. Effects of SGLT2 inhibition in human kidney proximal tubular cells-renoprotection in diabetic nephropathy? PLoS One. 2013;8:e54442
64. Gembardt F, Bartaun C, Jarzebska N, et al. The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension. Am J Physiol Renal Physiol. 2014;307:F317-F325
65. Shin SJ, Chung S, Kim SJ, et al. Effect of sodium-glucose co-transporter 2 inhibitor, Dapagliflozin, on renal renin-angiotensin system in an animal model of type 2 diabetes. PLoS One. 2016;11:e0165703
66. Wang XX, Levi J, Luo Y, et al. SGLT2 protein expression is increased in human diabetic nephropathy: SGLT2 protein inhibition decreases renal lipid accumulation, inflammation, and the development of nephropathy in diabetic mice. J Biol Chem. 2017;292:5335-5348
67. Wright EM, Hirsch JR, Loo DD, Zampighi GA. Regulation of Na+/glucose cotransporters. J Exp Biol. 1997;200:287-293
68. Walker J, Jijon HB, Diaz H, Salehi P, Churchill T, Madsen KL. 5-aminoimidazole-4-carboxamide riboside (AICAR) enhances GLUT2-dependent jejunal glucose transport: a possible role for AMPK. Biochem J. 2005;385:485-491
69. Thomas CC, Bakris G. Metformin nephrotoxicity insights: will they change clinical management? J Diabetes. 2014;6:111-112
70. Chagnac A, Weinstein T, Korzets A, Ramadan E, Hirsch J, Gafter U. Glomerular hemodynamics in severe obesity. Am J Physiol Renal Physiol. 2000;278:F817-F822
71. Hostetter TH, Lising M. National kidney disease education program. J Am Soc Nephrol. 2003;14:S114-S116
72. Du N, Peng H, Chao X, Zhang Q, Tian H, Li H. Interaction of obesity and central obesity on elevated urinary albumin-to-creatinine ratio. PLoS One. 2014;9:e98926