Reviews in Endocrine and Metabolic Disorders

, Volume 15, Issue 3, pp 197–207 | Cite as

Effects of GLP-1 in the Kidney

Article

Abstract

The incretin hormone, glucagon-like peptide-1 (GLP-1), stimulates insulin secretion and forms the basis of a new drug class for diabetes treatment. GLP-1 has several extra-pancreatic properties which include effects on kidney function. Although renal GLP-1 receptors have been identified, their exact localization and physiological role are incompletely understood. GLP-1 increases natriuresis through inhibition of the sodium-hydrogen ion exchanger isoform 3 in the proximal tubule. This may in part explain why GLP-1 receptor agonists have antihypertensive effects. Glomerular filtration rate is regulated by GLP-1, but the mechanisms are complex and may depend on e.g. glycaemic conditions. Atrial natriuretic peptide or the renin-angiotensin system may be involved in the signalling of GLP-1-mediated renal actions. Several studies in rodents have shown that GLP-1 therapy is renoprotective beyond metabolic improvements in models of diabetic nephropathy and acute kidney injury. Inhibition of renal inflammation and oxidative stress probably mediate this protection. Clinical studies supporting GLP-1-mediated renal protection exist, but they are few and with limitations. However, acute and chronic kidney diseases are major global health concerns and measures improving renal outcome are highly needed. Therefore, the renoprotective potential of GLP-1 therapy need to be thoroughly investigated in humans.

Keywords

Glucagon-like peptide-1 Renal Glomerular filtration rate Natriuresis Diabetic nephropathy Acute kidney injury 

Abbreviations

ANG2

angiotensin II

AKI

acute kidney injury

ANP

atrial natriuretic peptide

ARB

angiotensin II receptor blocker

CrCl

creatinine clearance

DN

diabetic nephropathy

DPP-4

dipeptidyl peptidase IV

EMA

European Medicine Agency

ESRD

end-stage renal disease

GLP-1

glucagon-like peptide-1

GLP-1R

glucagon-like peptide-1 receptor

GFR

glomerular filtration rate

mRNA

messenger ribonucleic acid

NHE3

Na+/H+ exchanger isoform 3

PKA

protein kinase A

RAS

renin-angiotensin system

RBF

renal blood flow

ROS

reactive oxygen species

SGLT2

sodium-glucose linked transporter 2

STZ

streptozotocin

T2DM

type 2 diabetes mellitus

TGF

tubuloglomerular feedback

Notes

Conflict of interest

J.S. has a PhD fellowship in a joint collaboration between Aarhus University Hospital and Novo Nordisk.

References

  1. 1.
    Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409–39.PubMedCrossRefGoogle Scholar
  2. 2.
    Vilsboll T, Agerso H, Krarup T, Holst JJ. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab. 2003;88(1):220–4. doi: 10.1210/jc.2002-021053.PubMedCrossRefGoogle Scholar
  3. 3.
    Meier JJ, Nauck MA, Kranz D, Holst JJ, Deacon CF, Gaeckler D, et al. Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. Diabetes. 2004;53(3):654–62.PubMedCrossRefGoogle Scholar
  4. 4.
    Bullock BP, Heller RS, Habener JF. Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor. Endocrinology. 1996;137(7):2968–78. doi: 10.1210/en.137.7.2968.PubMedGoogle Scholar
  5. 5.
    Körner M, Stöckli M, Waser B, Reubi JC. GLP-1 Receptor Expression in Human Tumors and Human Normal Tissues: Potential for In Vivo Targeting. J Nucl Med. 2007;48(5):736–43. doi: 10.2967/jnumed.106.038679.PubMedCrossRefGoogle Scholar
  6. 6.
    Vilsboll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. Bmj. 2012;344:d7771.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Wang B, Zhong J, Lin H, Zhao Z, Yan Z, He H, et al. Blood pressure-lowering effects of GLP-1 receptor agonists exenatide and liraglutide: a meta-analysis of clinical trials. Diabetes Obes Metab. 2013;15(8):737–49. doi: 10.1111/dom.12085.PubMedCrossRefGoogle Scholar
  8. 8.
    Nauck MA, Niedereichholz U, Ettler R, Holst JJ, Orskov C, Ritzel R, et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. The American journal of physiology. 1997;273(5 Pt 1):E981–8.PubMedGoogle Scholar
  9. 9.
    Mendis B, Simpson E, MacDonald I, Mansell P. Investigation of the haemodynamic effects of exenatide in healthy male subjects. Br J Clin Pharmacol. 2012;74(3):437–44. doi: 10.1111/j.1365-2125.2012.04214.x.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev. 2012;33(2):187–215. doi: 10.1210/er.2011-1052.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Holst JJ, Burcelin R, Nathanson E. Neuroprotective properties of GLP-1: theoretical and practical applications. Current medical research and opinion. 2011;27(3):547–58. doi: 10.1185/03007995.2010.549466.PubMedCrossRefGoogle Scholar
  12. 12.
    Gutzwiller JP, Tschopp S, Bock A, Zehnder CE, Huber AR, Kreyenbuehl M et al. Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men. J Clin Endocrinol Metab. 2004;89 (6):3055–61. doi: 10.1210/jc.2003-03140389/6/3055 [pii]
  13. 13.
    Skov J, Dejgaard A, Frokiaer J, Holst JJ, Jonassen T, Rittig S, et al. Glucagon-Like Peptide-1 (GLP-1): Effect on Kidney Hemodynamics and Renin-Angiotensin-Aldosterone System in Healthy Men. J Clin Endocrinol Metab. 2013;98(4):E664–71. doi: 10.1210/jc.2012-3855.PubMedCrossRefGoogle Scholar
  14. 14.
    Ritz E, Rychlik I, Locatelli F, Halimi S. End-stage renal failure in type 2 diabetes: A medical catastrophe of worldwide dimensions. Am J Kidney Dis. 1999;34(5):795–808. doi: 10.1016/s0272-6386(99)70035-1.PubMedCrossRefGoogle Scholar
  15. 15.
    Moreno C, Mistry M, Roman RJ. Renal effects of glucagon-like peptide in rats. Eur J Pharmacol. 2002;434(3):163–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Crajoinas RO, Oricchio FT, Pessoa TD, Pacheco BPM, Lessa LMA, Malnic G, et al. Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1. Am J Physiol Ren Physiol. 2011;301(2):F355–F63. doi: 10.1152/ajprenal.00729.2010.CrossRefGoogle Scholar
  17. 17.
    Fujita H, Morii T, Fujishima H, Sato T, Shimizu T, Hosoba M et al. The protective roles of GLP-1R signaling in diabetic nephropathy: possible mechanism and therapeutic potential. Kidney Int. 2013. doi: 10.1038/ki.2013.427.
  18. 18.
    Carraro-Lacroix LR, Malnic G, Girardi ACC. Regulation of Na+/H + exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells. Am J Physiol Ren Physiol. 2009;297(6):F1647–F55. doi: 10.1152/ajprenal.00082.2009.CrossRefGoogle Scholar
  19. 19.
    Kodera R, Shikata K, Kataoka HU, Takatsuka T, Miyamoto S, Sasaki M, et al. Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes. Diabetologia. 2011;54(4):965–78. doi: 10.1007/s00125-010-2028-x.PubMedCrossRefGoogle Scholar
  20. 20.
    Schlatter P, Beglinger C, Drewe J, Gutmann H. Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cells. Regul Pept. 2007;141(1–3):120–8. doi: 10.1016/j.regpep.2006.12.016.PubMedCrossRefGoogle Scholar
  21. 21.
    Pezeshki A, Muench GP, Chelikani PK. Short communication: expression of peptide YY, proglucagon, neuropeptide Y receptor Y2, and glucagon-like peptide-1 receptor in bovine peripheral tissues. J Dairy Sci. 2012;95(9):5089–94. doi: 10.3168/jds.2011-5311.PubMedCrossRefGoogle Scholar
  22. 22.
    Pyke C, Knudsen LB. The Glucagon-Like Peptide-1 Receptor—or Not? Endocrinology. 2013;154(1):4–8. doi: 10.1210/en.2012-2124.PubMedCrossRefGoogle Scholar
  23. 23.
    Panjwani N, Mulvihill EE, Longuet C, Yusta B, Campbell JE, Brown TJ, et al. GLP-1 receptor activation indirectly reduces hepatic lipid accumulation but does not attenuate development of atherosclerosis in diabetic male ApoE (−/−) mice. Endocrinology. 2013;154(1):127–39. doi: 10.1210/en.2012-1937.PubMedCrossRefGoogle Scholar
  24. 24.
    Yu M, Moreno C, Hoagland KM, Dahly A, Ditter K, Mistry M, et al. Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats. J Hypertens. 2003;21(6):1125–35.PubMedCrossRefGoogle Scholar
  25. 25.
    Thomson SC, Kashkouli A, Singh P. Glucagon-like peptide-1 receptor stimulation increases GFR and suppresses proximal reabsorption in the rat. Am J Physiol-Renal Physiol. 2013;304(2):F137–F44. doi: 10.1152/ajprenal.00064.2012.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Hirata K, Kume S. Araki S-i, Sakaguchi M, Chin-Kanasaki M, Isshiki K et al. Exendin-4 has an anti-hypertensive effect in salt-sensitive mice model. Biochemical and Biophysical Research. Communications. 2009;380(1):44–9.Google Scholar
  27. 27.
    Liu Q, Adams L, Broyde A, Fernandez R, Baron A, Parkes D. The exenatide analogue AC3174 attenuates hypertension, insulin resistance, and renal dysfunction in Dahl salt-sensitive rats. Cardiovasc Diabetol. 2010;9(1):32.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Rieg T, Gerasimova M, Murray F, Masuda T, Tang T, Rose M, et al. Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic mice. Am J Physiol Renal Physiol. 2012;303(7):F963–71. doi: 10.1152/ajprenal.00259.2012.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Larsen PJ, Fledelius C, Knudsen LB, Tang-Christensen M. Systemic administration of the long-acting GLP-1 derivative NN2211 induces lasting and reversible weight loss in both normal and obese rats. Diabetes. 2001;50(11):2530–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Kim M, Platt MJ, Shibasaki T, Quaggin SE, Backx PH, Seino S, et al. GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure. Nat Med. 2013;19(5):567–75. doi: 10.1038/nm.3128.PubMedCrossRefGoogle Scholar
  31. 31.
    Girardi AC, Fukuda LE, Rossoni LV, Malnic G, Reboucas NA. Dipeptidyl peptidase IV inhibition downregulates Na + − H + exchanger NHE3 in rat renal proximal tubule. Am J Physiol Renal Physiol. 2008;294(2):F414–22. doi: 10.1152/ajprenal.00174.2007.PubMedCrossRefGoogle Scholar
  32. 32.
    Gutzwiller JP, Hruz P, Huber AR, Hamel C, Zehnder C, Drewe J, et al. Glucagon-like peptide-1 is involved in sodium and water homeostasis in humans. Digestion. 2006;73(2–3):142–50. doi: 10.1159/000094334.PubMedCrossRefGoogle Scholar
  33. 33.
    Pacheco BP, Crajoinas RO, Couto GK, Davel AP, Lessa LM, Rossoni LV, et al. Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats. J Hypertens. 2011;29(3):520–8. doi: 10.1097/HJH.0b013e328341939d.PubMedCrossRefGoogle Scholar
  34. 34.
    Thomsen K. Lithium Clearance: A New Method for Determining Proximal and Distal Tubular Reabsorption of Sodium and Water. Nephron. 1984;37(4):217–23.PubMedCrossRefGoogle Scholar
  35. 35.
    Girardi AC, Di Sole F. Deciphering the mechanisms of the Na+/H + exchanger-3 regulation in organ dysfunction. American journal of physiology Cell physiology. 2012;302(11):C1569–87. doi: 10.1152/ajpcell.00017.2012.PubMedCrossRefGoogle Scholar
  36. 36.
    Girardi AC, Knauf F, Demuth HU, Aronson PS. Role of dipeptidyl peptidase IV in regulating activity of Na+/H + exchanger isoform NHE3 in proximal tubule cells. American journal of physiology Cell physiology. 2004;287(5):C1238–45. doi: 10.1152/ajpcell.00186.2004.PubMedCrossRefGoogle Scholar
  37. 37.
    Girardi AC, Degray BC, Nagy T, Biemesderfer D, Aronson PS. Association of Na (+)-H (+) exchanger isoform NHE3 and dipeptidyl peptidase IV in the renal proximal tubule. J Biol Chem. 2001;276(49):46671–7. doi: 10.1074/jbc.M106897200.PubMedCrossRefGoogle Scholar
  38. 38.
    Park CW, Kim HW, Ko SH, Lim JH, Ryu GR, Chung HW, et al. Long-Term Treatment of Glucagon-Like Peptide-1 Analog Exendin-4 Ameliorates Diabetic Nephropathy through Improving Metabolic Anomalies in db/dB Mice. J Am Soc Nephrol. 2007;18(4):1227–38. doi: 10.1681/asn.2006070778.PubMedCrossRefGoogle Scholar
  39. 39.
    Persson P, Hansell P, Palm F. Tubular reabsorption and diabetes-induced glomerular hyperfiltration. Acta Physiol (Oxf). 2010;200(1):3–10. doi: 10.1111/j.1748-1716.2010.02147.x.Google Scholar
  40. 40.
    Yu M, Moreno C, Hoagland KM, Dahly A, Ditter K, Mistry M, et al. Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats. J Hypertens. 2003;21(6):1125–35. doi: 10.1097/01.hjh.0000059046.65882.49.PubMedCrossRefGoogle Scholar
  41. 41.
    Varanasi A, Chaudhuri A, Dhindsa S, Arora A, Lohano T, Vora MR, et al. Durability of effects of exenatide treatment on glycemic control, body weight, systolic blood pressure, C-reactive protein, and triglyceride concentrations. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2011;17(2):192–200. doi: 10.4158/ep10199.or.CrossRefGoogle Scholar
  42. 42.
    Liu WJ, Xie SH, Liu YN, Kim W, Jin HY, Park SK, et al. Dipeptidyl Peptidase IV Inhibitor Attenuates Kidney Injury in Streptozotocin-Induced Diabetic Rats. J Pharmacol Exp Ther. 2012;340(2):248–55. doi: 10.1124/jpet.111.186866.PubMedCrossRefGoogle Scholar
  43. 43.
    Skov J, Holst JJ, Goetze JP, Frokiaer J, Christiansen JS. Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy males. Endocrine connections. 2013. doi: 10.1530/ec-13-0087.
  44. 44.
    Ishibashi Y, Matsui T, Ojima A, Nishino Y, Nakashima S, Maeda S, et al. Glucagon-like peptide-1 inhibits angiotensin II-induced mesangial cell damage via protein kinase A. Microvasc Res. 2012;84(3):395–8. doi: 10.1016/j.mvr.2012.06.008.PubMedCrossRefGoogle Scholar
  45. 45.
    Mima A, Hiraoka-Yamomoto J, Li Q, Kitada M, Li C, Geraldes P, et al. Protective effects of GLP-1 on glomerular endothelium and its inhibition by PKCbeta activation in diabetes. Diabetes. 2012;61(11):2967–79. doi: 10.2337/db11-1824.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    van der Zijl NJ, Moors CC, Goossens GH, Hermans MM, Blaak EE, Diamant M. Valsartan improves {beta}-cell function and insulin sensitivity in subjects with impaired glucose metabolism: a randomized controlled trial. Diabetes Care. 2011;34(4):845–51. doi: 10.2337/dc10-2224.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Wang HW, Mizuta M, Saitoh Y, Noma K, Ueno H, Nakazato M. Glucagon-like peptide-1 and candesartan additively improve glucolipotoxicity in pancreatic beta-cells. Metabolism. 2011;60(8):1081–9. doi: 10.1016/j.metabol.2010.11.004.PubMedCrossRefGoogle Scholar
  48. 48.
    Lu HL, Wang ZY, Huang X, Han YF, Wu YS, Guo X, et al. Excitatory regulation of angiotensin II on gastric motility and its mechanism in guinea pig. Regul Pept. 2011;167(2–3):170–6. doi: 10.1016/j.regpep.2011.01.004.PubMedCrossRefGoogle Scholar
  49. 49.
    Fogari R, Derosa G, Zoppi A, Rinaldi A, Lazzari P, Fogari E, et al. Comparison of the effects of valsartan and felodipine on plasma leptin and insulin sensitivity in hypertensive obese patients. Hypertension research : official journal of the Japanese Society of Hypertension. 2005;28(3):209–14. doi: 10.1291/hypres.28.209.CrossRefGoogle Scholar
  50. 50.
    Malm-Erjefalt M, Bjornsdottir I, Vanggaard J, Helleberg H, Larsen U, Oosterhuis B, et al. Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug metabolism and disposition: the biological fate of chemicals. 2010;38(11):1944–53. doi: 10.1124/dmd.110.034066.CrossRefGoogle Scholar
  51. 51.
    Simonsen L, Holst JJ, Deacon CF. Exendin-4, but not glucagon-like peptide-1, is cleared exclusively by glomerular filtration in anaesthetised pigs. Diabetologia. 2006;49(4):706–12. doi: 10.1007/s00125-005-0128-9.PubMedCrossRefGoogle Scholar
  52. 52.
    Vejakama P, Thakkinstian A, Lertrattananon D, Ingsathit A, Ngarmukos C, Attia J. Reno-protective effects of renin-angiotensin system blockade in type 2 diabetic patients: a systematic review and network meta-analysis. Diabetologia. 2012;55(3):566–78.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Rossing P, de Zeeuw D. Need for better diabetes treatment for improved renal outcome. Kidney Int Suppl. 2011;120:S28–32. doi: 10.1038/ki.2010.513.PubMedCrossRefGoogle Scholar
  54. 54.
    Ojima A, Ishibashi Y, Matsui T, Maeda S, Nishino Y, Takeuchi M et al. Glucagon-Like Peptide-1 Receptor Agonist Inhibits Asymmetric Dimethylarginine Generation in the Kidney of Streptozotocin-Induced Diabetic Rats by Blocking Advanced Glycation End Product–Induced Protein Arginine Methyltranferase-1 Expression. The American journal of pathology. 2013;182 (1):132–41. doi:http://dx.doi.org/ 10.1016/j.ajpath.2012.09.016.
  55. 55.
    Hendarto H, Inoguchi T, Maeda Y, Ikeda N, Zheng J, Takei R, et al. GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin-induced diabetic rats via protein kinase A-mediated inhibition of renal NAD (P)H oxidases. Metabolism. 2012;61(10):1422–34. doi: 10.1016/j.metabol.2012.03.002.PubMedCrossRefGoogle Scholar
  56. 56.
    Alter ML, Ott IM, von Websky K, Tsuprykov O, Sharkovska Y, Krause-Relle K, et al. DPP-4 inhibition on top of angiotensin receptor blockade offers a new therapeutic approach for diabetic nephropathy. Kidney & blood pressure research. 2012;36(1):119–30. doi: 10.1159/000341487.CrossRefGoogle Scholar
  57. 57.
    Kodera R, Shikata K, Takatsuka T, Oda K, Miyamoto S, Kajitani N et al. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes. Biochem Biophys Res Commun. 2013. doi: 10.1016/j.bbrc.2013.12.049.
  58. 58.
    Shiraki A, Oyama J, Komoda H, Asaka M, Komatsu A, Sakuma M, et al. The glucagon-like peptide 1 analog liraglutide reduces TNF-alpha-induced oxidative stress and inflammation in endothelial cells. Atherosclerosis. 2012;221(2):375–82. doi: 10.1016/j.atherosclerosis.2011.12.039.PubMedCrossRefGoogle Scholar
  59. 59.
    Liu L, Liu J, Wong WT, Tian XY, Lau CW, Wang YX, et al. Dipeptidyl peptidase 4 inhibitor sitagliptin protects endothelial function in hypertension through a glucagon-like peptide 1-dependent mechanism. Hypertension. 2012;60(3):833–41. doi: 10.1161/hypertensionaha.112.195115.PubMedCrossRefGoogle Scholar
  60. 60.
    Ishibashi Y, Nishino Y, Matsui T, Takeuchi M, Yamagishi S. Glucagon-like peptide-1 suppresses advanced glycation end product-induced monocyte chemoattractant protein-1 expression in mesangial cells by reducing advanced glycation end product receptor level. Metabolism. 2011;60(9):1271–7. doi: 10.1016/j.metabol.2011.01.010.PubMedCrossRefGoogle Scholar
  61. 61.
    Li W, Cui M, Wei Y, Kong X, Tang L, Xu D. Inhibition of the expression of TGF-beta1 and CTGF in human mesangial cells by exendin-4, a glucagon-like peptide-1 receptor agonist. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2012;30(3):749–57. doi: 10.1159/000341454.CrossRefGoogle Scholar
  62. 62.
    Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, et al. Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus. N Engl J Med. 2013;369(14):1317–26. doi: 10.1056/NEJMoa1307684.PubMedCrossRefGoogle Scholar
  63. 63.
    Zhang H, Zhang X, Hu C, Lu W. Exenatide reduces urinary transforming growth factor-beta1 and type IV collagen excretion in patients with type 2 diabetes and microalbuminuria. Kidney & blood pressure research. 2012;35(6):483–8. doi: 10.1159/000337929.CrossRefGoogle Scholar
  64. 64.
    Fujita H, Taniai H, Murayama H, Ohshiro H, Hayashi H, Sato S et al. DPP-4 inhibition with alogliptin on top of angiotensin II type 1 receptor blockade ameliorates albuminuria via up-regulation of SDF-1alpha in type 2 diabetic patients with incipient nephropathy. Endocrine journal. 2013.Google Scholar
  65. 65.
    Imamura S, Hirai K, Hirai A. The glucagon-like Peptide-1 receptor agonist, liraglutide, attenuates the progression of overt diabetic nephropathy in type 2 diabetic patients. Tohoku J Exp Med. 2013;231(1):57–61.PubMedCrossRefGoogle Scholar
  66. 66.
    Abd El Motteleb DM, Elshazly SM. Renoprotective effect of sitagliptin against hypertensive nephropathy induced by chronic administration of l-NAME in rats: Role of GLP-1 and GLP-1 receptor. Eur J Pharmacol. 2013;720(1–3):158–65. doi: 10.1016/j.ejphar.2013.10.033.PubMedCrossRefGoogle Scholar
  67. 67.
    Joo KW, Kim S, Ahn SY, Chin HJ, Chae DW, Lee J, et al. Dipeptidyl peptidase IV inhibitor attenuates kidney injury in rat remnant kidney. BMC Nephrol. 2013;14:98. doi: 10.1186/1471-2369-14-98.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet. 2012;380(9843):756–66. doi: 10.1016/s0140-6736(11)61454-2.PubMedCrossRefGoogle Scholar
  69. 69.
    Lameire NH, Bagga A, Cruz D, De Maeseneer J, Endre Z, Kellum JA, et al. Acute kidney injury: an increasing global concern. Lancet. 2013;382(9887):170–9. doi: 10.1016/s0140-6736(13)60647-9.PubMedCrossRefGoogle Scholar
  70. 70.
    Yang H, Li H, Wang Z, Shi Y, Jiang G, Zeng F. Exendin-4 ameliorates renal ischemia-reperfusion injury in the rat. The Journal of surgical research. 2013;185(2):825–32. doi: 10.1016/j.jss.2013.06.042.PubMedCrossRefGoogle Scholar
  71. 71.
    Glorie LL, Verhulst A, Matheeussen V, Baerts L, Magielse J, Hermans N, et al. DPP4 inhibition improves functional outcome after renal ischemia-reperfusion injury. Am J Physiol Renal Physiol. 2012;303(5):F681–8. doi: 10.1152/ajprenal.00075.2012.PubMedCrossRefGoogle Scholar
  72. 72.
    Vaghasiya J, Sheth N, Bhalodia Y, Manek R. Sitagliptin protects renal ischemia reperfusion induced renal damage in diabetes. Regul Pept. 2011;166(1–3):48–54. doi: 10.1016/j.regpep.2010.08.007.PubMedCrossRefGoogle Scholar
  73. 73.
    Chen YT, Tsai TH, Yang CC, Sun CK, Chang LT, Chen HH, et al. Exendin-4 and sitagliptin protect kidney from ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction. J Transl Med. 2013;11(1):270. doi: 10.1186/1479-5876-11-270.PubMedCrossRefGoogle Scholar
  74. 74.
    Katagiri D, Hamasaki Y, Doi K, Okamoto K, Negishi K, Nangaku M et al. Protection of Glucagon-Like Peptide-1 in Cisplatin-Induced Renal Injury Elucidates Gut-Kidney Connection. J Am Soc Nephrol. 2013. doi: 10.1681/asn.2013020134.
  75. 75.
    Linnebjerg H, Kothare PA, Park S, Mace K, Reddy S, Mitchell M, et al. Effect of renal impairment on the pharmacokinetics of exenatide. Br J Clin Pharmacol. 2007;64(3):317–27. doi: 10.1111/j.1365-2125.2007.02890.x.PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Davidson JA, Brett J, Falahati A, Scott D. Mild renal impairment and the efficacy and safety of liraglutide. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2011;17(3):345–55. doi: 10.4158/ep10215.ra.CrossRefGoogle Scholar
  77. 77.
    Jacobsen LV, Hindsberger C, Robson R, Zdravkovic M. Effect of renal impairment on the pharmacokinetics of the GLP-1 analogue liraglutide. Br J Clin Pharmacol. 2009;68(6):898–905. doi: 10.1111/j.1365-2125.2009.03536.x.PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Idorn T, Knop FK, Jorgensen M, Jensen T, Resuli M, Hansen PM et al. Safety and efficacy of liraglutide in patients with type 2 diabetes and end-stage renal disease: protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded, parallel intervention study. BMJ Open. 2013;3 (4). doi: 10.1136/bmjopen-2013-002764.
  79. 79.
    Scheen AJ. Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010;12(8):648–58. doi: 10.1111/j.1463-1326.2010.01212.x.PubMedCrossRefGoogle Scholar
  80. 80.
    Weise WJ, Sivanandy MS, Block CA, Comi RJ. Exenatide-associated ischemic renal failure. Diabetes Care. 2009;32(2):e22–3. doi: 10.2337/dc08-1309.PubMedCrossRefGoogle Scholar
  81. 81.
    Narayana SK, Talab SK, Elrishi MA. Liraglutide-induced acute kidney injury. Practical Diabetes. 2012;29(9):380–2. doi: 10.1002/pdi.1727.CrossRefGoogle Scholar
  82. 82.
    Filippatos TD, Elisaf MS. Effects of glucagon-like peptide-1 receptor agonists on renal function. World journal of diabetes. 2013;4(5):190–201. doi: 10.4239/wjd.v4.i5.190.PubMedCentralPubMedGoogle Scholar
  83. 83.
    Abdul-Ghani MA, Norton L, Defronzo RA. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr Rev. 2011;32(4):515–31. doi: 10.1210/er.2010-0029.PubMedCrossRefGoogle Scholar
  84. 84.
    Thomson SC, Rieg T, Miracle C, Mansoury H, Whaley J, Vallon V, et al. Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat. Am J Physiol Regul Integr Comp Physiol. 2012;302(1):R75–83. doi: 10.1152/ajpregu.00357.2011.PubMedCentralPubMedCrossRefGoogle Scholar
  85. 85.
    Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A et al. The Renal Hemodynamic Effect of SGLT2 Inhibition in Patients with Type 1 Diabetes. Circulation. 2013. doi: 10.1161/circulationaha.113.005081.
  86. 86.
    Lonborg J, Vejlstrup N, Kelbaek H, Botker HE, Kim WY, Mathiasen AB, et al. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2012;33(12):1491–9. doi: 10.1093/eurheartj/ehr309.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Endocrinology and Internal MedicineAarhus University HospitalAarhusDenmark
  2. 2.Novo Nordisk A/SBagsvaerdDenmark

Personalised recommendations