Kidney in diabetes: From organ damage target to therapeutic target

Current Drug Metabolism

Volumn 12, Issue 7, 2011, Pages 658-666

  Salvatore, Teresa ^a   Carbonara, Ornella ^a   Cozzolino, Domenico ^a   Torella, Roberto ^a   Nasti, Rodolfo ^a   Lascar, Nadia ^a   Sasso, Ferdinando Carlo ^a  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

Author keywords

Antidiabetic drugs; Dapagliflozin; Kidney; SGLT2 inhibitors; Sodium glucose cotransporters; Type 2 diabetes.

Indexed keywords

ANTIDIABETIC AGENT; ASP 1941; BI 10773; CANAGLIFLOZIN; DAPAGLIFLOZIN; HEMOGLOBIN A1C; ISIS 388626; PHLORIZIN; SODIUM GLUCOSE COTRANSPORTER 2; UNCLASSIFIED DRUG;

BRUSH BORDER; DRUG HALF LIFE; DRUG STRUCTURE; ENERGY BALANCE; GLUCOSE ABSORPTION; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; INSULIN RELEASE; KIDNEY PROXIMAL TUBULE; NON INSULIN DEPENDENT DIABETES MELLITUS; REVIEW; URINARY EXCRETION; WEIGHT GAIN;

ANIMALS; BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; DRUG DELIVERY SYSTEMS; HUMANS; HYPOGLYCEMIC AGENTS; KIDNEY; SODIUM-GLUCOSE TRANSPORTER 2;

EID: 79961083208     PISSN: 13892002     EISSN: 18755453     Source Type: Journal    
DOI: 10.2174/138920011796504509     Document Type: Review

References (85)

1. Prentki, M.; Nolan, C.J. Islet β-cell failure in type 2 diabetes. J. Clin. Invest., 2006, 116(7),1802-1812. (Pubitemid 44033300)
2. UK Prospective Diabetes Study (UKPDS) Group. Intensive bloodglucose control with sulphonylurea or insulin compared with conventional treatment and risks of complications in patients with type 2 diabetes (UKPDS 33). Lancet, 1998, 352(9131), 837-853.
3. 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). Lancet, 1998, 352(9131), 854-865.
4. Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes treatment on the development and progression of long-term complications in insulin-dependent diabetes mellitus: the Diabetes Control and Complications Trial. N. Engl. J. Med., 1993, 329(14), 977-86.
5. American Diabetes Association: Standards of medical care in diabetes 2010. Diabetes Care, 2010, 33(Suppl. 1), S11-S61.
6. Nathan, D.M.; Buse, J.B.; Davidson, M.B.; Ferrannini, E.; Holman, R.R.; Sherwin, R.; Zinman, B. Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia, 2009, 52(1), 17-30.
7. Dluhy, R.G.; McMahon, G.T. Intensive glycemic control in the ACCORD and ADVANCE trials. N. Engl. J. Med., 2008, 358(24), 2630-2633. (Pubitemid 351831365)
8. Gaede, P.; Vedel, P.; Larsen, N.; Jensen, G.V.; Parving ,H.H.; Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N. Engl. J. Med., 2003, 348(5), 383-393. (Pubitemid 36159355)
9. Handlon, A.L. Sodium glucose co-transporter 2 (SGLT-2) inhibitors as potential antidiabetic agents. Expert Opin. Ther. Pat., 2005, 15(11), 1531-1540. (Pubitemid 41671615)
10. Isaji, M. Sodium-glucose cotransporter inhibitors for diabetes. Curr. Opin. Investig. Drugs, 2007, 8(4), 285-292. (Pubitemid 46557988)
11. Jabbour, S.A.; Goldstein, B.J. Sodium-glucose cotransporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes. Int. J. Clin. Pract., 2008, 62(8), 1279-1284. (Pubitemid 351977622)
12. Stumvoll, M.; Meyer, C.; Mitrakou, A.; Nadkarni, V; Gerich, J.E. Renal glucose production and utilization: new aspects in humans. Diabetologia, 1997, 40(7), 749-757. (Pubitemid 27306951)
13. Gerich, J.E. Role of the kidney in normal glucose homeostasis and in hyperglycaemia of diabetes mellitus: therapeutic implication. Diabet. Med., 2010, 27(2), 136-142.
14. Meyer, C.; Dostou, J.M.; Welle, S.L.; Gerich, J.E. Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis. Am. J. Physiol. Endocrinol. Metab., 2002, 282(2), E419-E427. (Pubitemid 34654813)
15. Meyer, C.; Dostou, J.M.; Nadkarni, V.; Gerich J. Effects of physiological hyperinsulinemia on systemic, renal, and hepatic substrate metabolism. Am. J. Physiol., 1998, 275(6 Pt 2), F915-F921.
16. Dinneen, S.; Gerich, J.E.; Rizza, R. Carbohydrate metabolism in non-insulin-dependent diabetes mellitus. N. Engl. J. Med., 1992, 327(10), 707-713.
17. DeFronzo, R. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes, 1988, 37(6), 667-687.
18. Bearn, A.G.; Billing, B.H.; Sherlock, S. Hepatic glucose output and hepatic insulin sensitivity in diabetes mellitus. Lancet, 1951, 2(6686), 698-701.
19. Carlsten, B.; Hallgren, B.; Jagenburg, R.; Svanborg, A.; Werkö, L. Arterio-hepatic venous differences of free fatty acids and amino acids. Studies in patients with diabetes or essential hypercholesterolemia, and in healthy individuals. Acta. Med. Scand., 1967, 181(2), 199-207.
20. Felig, P.; Wahren, J.; Hendler, R. Influence of maturity-onset diabetes on splanchnic glucose balance after oral glucose ingestion. Diabetes, 1978, 27(2):121-126. (Pubitemid 8294837)
21. Waldhäusl, W.; Bratusch-Marrain, P.; Gasić, S.; Korn, A.; Nowotny, P. Insulin production rate, hepatic insulin retention and splanchnic metabolism after oral glucose ingestion in hyperinsulinemic type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia,1982, 23(1), 6-15. (Pubitemid 12078029)
22. Meyer, C.; Stumvoll, M.; Nadkarni, V.; Dostou, J.; Mitrakou, A.; Gerich, J. Abnormal renal and hepatic glucose metabolism in type 2 diabetes mellitus. J. Clin. Invest., 1998, 102(3):619-624. (Pubitemid 28376164)
23. Kone, B.C. Metabolic basis of solute transport. In: Brenner BM, ed. Brenner & Rector's The Kidney, 8th ed. Philadelphia: Saunders, Elsevier, 2007, 130-146.
24. Meyer, C.; Woerle, H.J.; Dostou, J.M.; Welle, S.L.; Gerich, J.E. Abnormal renal, hepatic, and muscle glucose metabolism following glucose ingestion in type 2 diabetes. Am. J. Physiol. Endocrinol. Metab., 2004, 287(6), E1049-E1056. (Pubitemid 39491945)
25. Cersosimo, E.; Garlick, P.; Ferretti, J. Insulin regulation of renal glucose metabolism in humans. Am. J. Physiol. Endocrinol. Metab., 1999, 276(1 Pt 1), E78-E84. (Pubitemid 29065596)
26. Wright, E.M. Renal Na+ -glucose co-transporters. Am. J. Physiol. Renal Physiol., 2001, 280(1), F10-F18.
27. Chao, E.C.; Henry, R.R. SGLT2 inhibition - a novel strategy for diabetes treatment. Nat. Rev. Drug Discov., 2010, 9(7), 551-559.
28. Moe, O.W.; Wright, S.H.; Palacin, M. Renal handling of organic solutes. In: Brenner BM, ed. Brenner & Rector's The Kidney, 8th ed. Philadelphia: Saunders, Elsevier, 2007, 214-247.
29. Ganong, W.F. Formation and excretion of urine. In: Review of Medical Physiology by Ganong W.F., McGraw-Hill Medical Publishing, 22nd ed., 2005, 699-734.
30. Rave, K.; Nosek, L.; Posner, J.; Heise, T.; Roggen, K.; van Hoogdalem, E-J. Renal glucose excretion as a function of blood glucose concentration in subjects with type 2 diabetes-results of a hyperglycaemic glucose clamp study. Nephrol. Dial. Transplant., 2006, 21(8), 2166-2171. (Pubitemid 44295041)
31. Abdul-Ghani, M.A.; DeFronzo, R.A. Inhibition of renal glucose reabsorption: a novel strategy for achieving glucose control in type 2 diabetes mellitus. Endocr. Pract., 2008, 14(6), 782-790.
32. Noonan, W.T.; Shapiro, V.M.; Banks, R.O. Renal glucose reabsorption during hypertonic glucose infusion in female streptozotocin- induced diabetic rats. Life Sci., 2001, 68(26), 2967-2977. (Pubitemid 32453264)
33. Dominguez, J.H.; Camp, K.; Maianu, L.; Feister, H.; Garvey, W.T. Molecular adaptations of GLUT1 and GLUT2 in renal proximal tubules of diabetic rats. Am. J. Physiol., 1994, 266(2 Pt 2), F283-F290.
34. Kamran, M.; Peterson, R.G.; Dominguez, J.H. Overexpression of GLUT2 gene in renal proximal tubules of diabetic Zucker rats. J. Am. Soc. Nephrol., 1997, 8(6), 943-948. (Pubitemid 27427241)
35. Mogensen, C.E. Maximum tubular reabsorption capacity for glucose and renal hemodynamics during rapid hypertonic glucose infusion in normal and diabetic subjects. Scand. J. Clin. Lab. Invest., 1971, 28(1), 101-109.
36. Nair, S.; Wilding, J.P. Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus. J. Clin. Endocrinol. Metab., 2010, 95(1), 34-42.
37. Elsas, L.J.; Rosenberg, L.E. Familial renal glycosuria: a genetic reappraisal of hexose transport by kidney and intestine. J. Clin. Invest., 1969, 48(10), 1845-1854.
38. Elsas, L.J; Hillman, R.E.; Patterson, J.H.; Rosenberg, L.E. Renal and intestinal hexose transport in familial glucose-galactose malabsorption. J. Clin. Invest., 1970, 49(3), 576-585.
39. Ganapathy V.; Thangaraju M.; Gopal E.; Martin P.M.; Itagaki S.; Miyauchi S.; Prasad P.D. Sodium-coupled monocarboxylate transporters in normal tissues and in cancer. AAPS J., 2008, 10, 193-199.
40. Kasahara, M.; Maeda, M.; Hayashi, S.; Mori, Y.; Abe, T. A missense mutation in the Na+/glucose co-transporter gene SGLT1 in a patient with congenital glucose-galactose malabsorption: normal trafficking but inactivation of the mutant protein. Biochim. Biophys. Acta, 2001, 1536(2-3), 141-147. (Pubitemid 32530813)
41. Wright, E.M.; Hirayama, B.A.; Loo,D.F. Active sugar transport in health and disease. J. Intern. Med., 2007, 261(1), 32-43. (Pubitemid 46046470)
42. Chen, J.; Feder, J.; Neuhaus, I.; Whaley J.M. Tissue expression profiling of the sodium-glucose co-transporter (SGLT) family: implication for targeting SGLT2 in type 2 diabetes patients (2493- PO). Diabetes 2008; 57 (Suppl 1): A682.
43. Zhou, L.; Cryan, E.V.; D'Andrea, M.R.; Belkowski, S.; Conway, B.R.; Demarest, K.T. Human cardiomyocytes express high level of Na+/glucose cotransporter 1 (SGLT1). J. Cell. Biochem., 2003, 90(2), 339-346. (Pubitemid 37222202)
44. Li, H.; Gu, Y.; Zhang, Y.; Lucas, M.J.; Wang, Y. High glucose levels down-regulate glucose transporter expression that correlates with increased oxidative stress in placental trophoblast cells in vitro. J. Soc. Gynecol. Invest., 2004, 11(2), 75-81. (Pubitemid 38229734)
45. Pajor, A.M.; Randolph, K.M.; Kerner, S.A.; Smith, C.D. Inhibitor binding in the human renal low- and high-affinity Na+/glucose cotransporters. J. Pharmacol. Exp. Ther., 2008, 324(3), 985-991. (Pubitemid 351397847)
46. van den Heuvel, L.P.; Assink, K.; Willemsen, M.; Monnens, L. Autosomal recessive renal glucosuria attributable to a mutation in the sodium glucose cotransporter (SGLT2). Hum. Genet., 2002. 111(6), 544-547. (Pubitemid 36075086)
47. Santer, R.; Kinner, M.; Lassen, C.L.; Schneppenheim, R.; Eggert, P.; Bald, M.; Brodehl, J.; Daschner, M.; Ehrich, J.H.; Kemper, M.; Li Volti, S.; Neuhaus, T.; Skovby, F.; Swift, P.G.; Schaub, J.; Klaerke, D. Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J. Am. Soc. Nephrol., 2003, 14(11), 2873-2882. (Pubitemid 37305650)
48. Elsas, L.J.; Rosenberg, L.E. Familial renal glycosuria: a genetic reappraisal of hexose transport by kidney and intestine. J. Clin. Invest., 1969, 48(10),1845-1854.
49. Elsas, L.J.; Busse, D.; Rosenberg, L.E. Autosomal recessive inheritance of renal glycosuria. Metabolism, 1971, 20(10), 968-975.
50. Calado, J.; Sznajer, Y.; Metzger, D.; Rita, A.; Hogan, M.C.; Kattamis, A.; Scharf, M.; Tasic, V.; Greil, J.; Brinkert, F.; Kemper, M.J.; Santer, R. Twenty-one additional cases of familial renal glucosuria: absence of genetic heterogeneity, high prevalence of private mutations and further evidence of volume depletion. Nephrol. Dial. Transplant., 2008, 23(12), 3874-3879.
51. Vallon, V.; Platt, K.A.; Cunard, R.; Schroth, J.; Whaley, J.; Thomson, S.C.; Koepsell, H.; Rieg, T. SGLT2 mediates glucose reabsorption in the early proximal tubule. J. Am. Soc. Nephrol., 2011, 22(1), 104-12.
52. Rahmoune, H.; Thompson, P.W.; Ward, J.M.; Smith, C.D.; Hong, G.; Brown, J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes, 2005, 54(12), 3427-3434. (Pubitemid 43334332)
53. Kamran, M.; Peterson, R.G.; Dominguez, J.H. Overexpression of GLUT2 gene in renal proximal tubules of diabetic Zucker rats. J. Am. Soc. Nephrol., 1997, 8(6), 943-948. (Pubitemid 27427241)
54. Dominguez, J.H.; Camp, K.; Maianu, L.; Feister, H.; Garvey, W.T. Molecular adaptations of GLUT1 and GLUT2 in renal proximal tubules of diabetic rats. Am. J. Physiol., 1994, 266(2 Pt 2), F283-F290.
55. Chin, E.; Zamah, A.M.; Landau, D.; Grønbcek, H.; Flyvbjerg, A.; LeRoith, D.; Bondy, C.A. Changes in facilitative glucose transporter messenger ribonucleic acid levels in the diabetic rat kidney. Endocrinology, 1997, 138(3), 1267-1275. (Pubitemid 27089786)
56. Menzel, R.; Kaisaki, P.J.; Rjasanowski, I.; Heinke P.; Kerner, W.; Menzel, S. A low renal threshold for glucose in diabetic patients with a mutation in the hepatocyte nuclear factor-1a (HNF-1a) gene. Diabet. Med., 1998, 1, 816-820. (Pubitemid 28451949)
57. Pontoglio, M.; Prié, D.; Cheret, C.; Doyen, A.; Leroy, C.; Froguel, P.; Velho, G.; Yaniv, M.; Friedlander, G. HNF1alpha controls renal glucose reabsorption in mouse and man. EMBO Rep., 2000, 1(4), 359-65.
58. Lee, Y.J.; Lee, Y.J.; Han, H.J. Regulatory mechanisms of Na(+)/glucose cotransporters in renal proximal tubule cells. Kidney Int. Suppl., 2007, (106), S27-S35. (Pubitemid 47172558)
59. Bautista, R.; Manning, R.; Martinez, F.; Avila-Casado, Mdel C.; Soto, V.; Medina, A.; Escalante, B. Angiotensin II-dependent increased expression of Na+-glucose cotransporter in hypertension. Am. J. Physiol. Renal Physiol., 2004, 286(1), F127-F133. (Pubitemid 38045050)
60. Asano, T.; Anai, M.; Sakoda, H.; Fujishiro, M.; Ono, H.; Kurihara, H.; Uchijima, Y. SGLT as a therapeutic target. Drugs Fut., 2004, 29(5), 461-466. (Pubitemid 38997624)
61. Asano, T.; Ogihara, T.; Katagiri, H.; Sakoda, H.; Ono, H.; Fujishiro, M.; Anai, M.; Kurihara, H.; Uchijima, Y. Glucose transporter and Na+ ? glucose cotransporter as molecular targets of antidiabetic drugs. Curr. Med. Chem., 2004, 11(20), 2717-2724. (Pubitemid 39255559)
62. Ehrenkranz, J.R.; Lewis, N.G.; Kahn, C.R.; Roth, J. Phlorizin: a review. Diabetes. Metab. Res. Rev., 2005, 21(1), 31-38.
63. Rossetti, L.; Smith, D.; Shulman, G.I.; Papachristou, D.; DeFronzo, R.A. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J. Clin. Invest., 1987, 79(5), 1510-1515. (Pubitemid 17099657)
64. +- glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes, 1999, 48(9), 1794-1800. (Pubitemid 29415199)
65. Seidner, G.; Alvarez, M.G.; Yeh, J.I.; O'Driscoll, K.R.; Klepper, J.; Stump, T.S.; Wang, D.; Spinner, N.B.; Birnbaum, M.J.; De Vivo, D.C. GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier. Nat. Genet., 1998, 18(2), 188-191. (Pubitemid 28082472)
66. Rossetti, L.; Shulman, G.I.; Zawalich, W.; DeFronzo, R.A. Effect of chronic hyperglycemia on in vivo insulin secretion in partially pancreatectomized rats. J. Clin. Invest., 1987, 80(4), 1037-1044. (Pubitemid 18075639)
67. Kahn, B.B.; Shulman, G.I.; DeFronzo, R.A.; Cushman, S.W.; Rossetti, L. Normalization of blood glucose in diabetic rats with phlorizin treatment reverses insulin-resistant glucose transport in adipose cells without restoring glucose transporter gene expression. J. Clin. Invest., 1991, 87(2), 561-570.
68. [No authors listed] Dapagliflozin: BMS 512148; BMS-512148. Drugs R. D., 2010; 10(1): 47-54.
69. Han, S.; Hagan, D.L.; Taylor, J.R.; Xin, L.; Meng, W.; Biller, S.A.; Wetterau, J.R.; Washburn, W.N.; Whaley, J.M. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes, 2008,57(6), 1723-1729.
70. Meng, W.; Ellsworth, B.A.; Nirschl, A.A.; McCann, P.J.; Patel, M.; Girotra, R.N.; Wu, G.; Sher, P.M.; Morrison, E.P.; Biller, S.A.; Zahler, R.; Deshpande, P.P.; Pullockaran, A.; Hagan, D.L.; Morgan, N.; Taylor, J.R.; Obermeier, M.T.; Humphreys, W.G.; Khanna, A.; Discenza, L.; Robertson, J.G.; Wang, A.; Han, S.; Wetterau, J.R.; Janovitz, E.B.; Flint, O.P.; Whaley, J.M.; Washburn, W.N. Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J. Med. Chem., 2008, 51(5), 1145-1149. (Pubitemid 351480378)
71. Komoroski, B.; Vachharajani, N.; Boulton, D.; Kornhauser, D.; Geraldes, M.; Li, L.; Pfister, M. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin. Pharmacol. Ther., 2009, 85(5), 520-526.
72. Komoroski, B.; Vachharajani, N.; Feng, Y.; Li, L.; Kornhauser, D.; Pfister, M. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin. Pharmacol. Ther., 2009, 85(5):513-519.
73. List, J.F.; Woo, V.; Morales, E.; Tang, W.; Fiedorek, F.T. Sodiumglucose co-transport inhibition with dapagliflozin in type 2 diabetes mellitus. Diabetes Care, 2009, 32(4), 650-657.
74. Ferrannini, E.; Jimenez Ramos, S.; Salsali, A.; Tang, W.; List, J.F. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, doubleblind, placebo-controlled, phase III trial. Diabetes Care, 2010, 33(10), 2217-2224.
75. Wilding, J.P.; Norwood, P.; T'joen, C.; Bastien, A.; List, J.F.; Fiedorek, F.T. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care, 2009, 32(9), 1656-1662.
76. Bailey, C.J.; Gross, J.L.; Pieters, A.; Bastien, A.; List, J.F. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet, 2010, 375(9733), 2223-2233.
77. Zhang, L; Feng, Y.; List, J.; Kasichayanula, S.; Pfister, M. Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight. Diabetes Obes. Metab., 2010, 12(6), 510-516.
78. Rosenstock, J.; Arbit, D.; Usiskin, K.; Capuano, G.; Canovatchel, W. Canagliflozin, an inhibitor of sodium glucose co-transporter 2 (SGLT2), improves glycemic control and lowers body weight in subjects with type 2 diabetes (T2D) on metformin. Orlando: American Diabetes Association (ADA), 70th Scientific Sessions, 2010, 77-OR.
79. Wancewicz, E.V.; Siwkowski, A.; Meibohm, B.; Yates, C.R.; Pearce, M.; Matson, J.; Booten, S.;, Murray. S.F.; Hung, G.; Geary, R.S.; Bhanot, S.; Mon, B.P. Long term safety and efficacy of ISIS 388626, an optimized SGLT2 antisense inhibitor, in multiple diabetic and euglycemic species.San Francisco: American Diabetes Association (ADA), 68th Scientific Sessions, 2008, 334-OR.
80. Bhanot, S.; Murray, S.F.; Booten, S.L.; Chakravarty, K.; Zanardi, T.; Henry, S.; Watts, L.M.; Wancewicz, E.V.; Siwkowski, A.; Monia, B.P. ISIS 388626, an SGLT2 antisense drug, causes robust and sustained glucosuria in multiple species and is safe and welltolerated. New Orleans: American Diabetes Association (ADA), 69th Scientific Sessions, 2009, 328-OR.
81. Geerlings, S.E.; Brouwer, E.C.; Van Kessel, K.C.P.M.; Gaastra, W.; Stolk, R.P.; Hoepelman, A.I. Cytokine secretion is impaired in women with diabetes mellitus. Eur. J. Clin. Invest., 2000, 30(11), 995-1001.
82. Brown, J.S.; Wessels, H.; Chancellor, M.B.; Howards, S.S.; Stamm, W.E.; Stapleton, A.E.; Steers, W.D.; Van Den Eeden, S.K.; McVary, K.T. Urological complications of diabetes. Diabetes Care, 2005, 28(1), 177-185.
83. Hoepelman, A.I.; Meiland, R.; Geerlings, S.E. Pathogenesis and management of bacterial urinary tract infections in adult patients with diabetes mellitus. Int. J. Antimicrob. Agents, 2003, 22(Suppl 2), 35-43.
84. Geerlings, S.E.; Stolk, R.P.; Camps, M.J.; Netten, P.M.; Collet, T.J.; Hoepelman, A.I. Risk factors for symptomatic urinary tract infection in women with diabetes. Diabetes Care, 2000, 23(12), 1737-1741.
85. Kanai, Y.; Lee, W.S.; You, G.; Brown, D.; Hediger, M.A. The human kidney low affinity Na+ ? glucose cotransporter SGLT2. J. Clin. Invest., 1994, 93(1), 397-404.