MOLECULAR MECHANISMS OF FUNCTIONING RENAL TUBULES IN DIABETES MELLITUS: DECISION ON A NEW STRATEGY OF PROPHYLACTICS AND TREATMENT OF DIABETIC NEPHROPATHY
https://doi.org/10.24884/1561-6274-2008-12-2-29-35
Abstract
Cause-effect relations formed in the process of the development of diabetic nephropathy, dynamics and mechanisms of impairments of the tubular system were analyzed which by means of tubule-glomerular feedback can induce progress of the pathological process in renal corpuscles and in a matter of fact, determine the terms of manifestation of renal dysfunction in diabetes mellitus. At the same time the state of the tubule-interstitial apparatus of the kidney aggravated in dysfunction ofthe vascular glomerules due to the elevation of the volumetric loading of the tubules in hyperfusion of the nephrons, progress of proteinuria and increase production and filtration of cytokines. The presented facts open a new page in molecular biology of transport processes in the kidney, in particular with diabetes mellitus. The elucidation of the mechanisms of molecular remodeling of the renal; tubules, induced by pathogenetic factors of diabetes mellitus allows the strategy of diagnosis of diabetic nephropathy to be developed at the preclinical stage and to determine a new stratery of prophylactics and correction of tubular dysfunction in this condition.
About the Authors
E. F. Barinov
Донецкий национальный медицинский университет им. М. Горького
Ukraine
Ukraine
O. N. Sulaeva
Донецкий национальный медицинский университет им. М. Горького
Ukraine
Ukraine
References
1. Нефрология. Под ред. И.Е. Тареевой. М, 2000: 448-453
2. Ossman SS. Diabetic Nephropathy: Where we have been and where we are going. Diabetes Spectrum 2006; 19: 153-156
3. Wei P, Lane PH, Lane JT, Padanilam BJ. Glomerular structural and functional changes in a high fat diet mousy model of early stages Type 2 diabetes. Diabetologia 2004; 47: 1541-1549
4. Rebsomen L, Raccah D, Tsimaratos M. Diabetes mellitus and renal tubule functions. Nephrol Ther 2006; 2 [Suppl 1]: S28-31
5. Evangelista C, Rizzo M, Cantone A. Glomerulo-tubular balance in diabetes mellitus: molecular evidence and clinical consequences. G Ital Nefro 2006; 23 [Suppl 34]: S16-20
6. Vallon V, Richter K, Blantz RC et al. Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption. J Am Soc Nephrol 1999; 10 (12): 2569-2576
7. Vervoort G, Veldman B, Berden JH. Glomerular hyperfiltration in type 1 diabetes mellitus results from primary changes in proximal tubular sodium handling without changes in volume expansion. Eur J Clin Invest 2005; 35 (5): 330-336
8. Rajic M, Ilic S, Vlajkovic M et al. Radionuclide staging of renal function in type 1 diabetes mellitus. Ren Fail 2007; 29 (6): 685-691
9. Levine DZ, Iacovitti M, Robertson SJ, Mokhtar GA. Modulation of single-nephron GFR in the db/db mouse model of type 2 diabetes mellitus. Am J Physiol Regul Integr Comp Physiol 2006; 290 (4): R975-R981
10. Futrakul N, Vongthavarawat V, Sirisalipotch S. Tubular dysfunction and hemodynamic alteration in normoalbuminuric type 2 diabetes. Clin Hemorheol Microcirc 2005; 32 (1): 59-65
11. Suanarunsawat T, Klongpanichapak S, Chaiyabutr N. Role of nitric oxide in renal function in rats with short and prolonged periods of streptozotocin-induced diabetes. Diabetes Obes Metab 1999; 1 (6): 339-346
12. Satriano J, Vallon V. Primary kidney growth and its consequences at the onset of diabetes mellitus. Amino Acids 2006; 31 (1): 1-9
13. Siragy HM. Angiotensin II compartmentalization within the kidney: effects of salt diet and blood pressure alterations. Curr Opin Nephrol Hypertens 2006; 15 (1): 50-53
14. Zhang Y, Wada J. Collectrin, a homologue of ACE2, its transcriptional conrol and functional perspectives. Biochem Biophys Res Commun 2007; 363 (1): 1-5
15. Ina K, Kitamura H, Nagai K et al. Ultrastructural and functional changes of the proximal tubular epithelial cells in the renal cortex from spontaneously diabetic KKAy mice. J Electron Microsc 1999; 48 (4): 443-448
16. Klisic J, Nief V, Reyes L, Ambuhl PM. Acute and chronic regulation of the renal Na/H(+) exchanger NHE3 in rats with STZ-induced diabetes mellitus. Nephron Physiol 2005; 102 (2): p27-p35
17. Capasso G, Evangelista C, Zacchia M. Acid-base transport in Henle’s loop: the effects of reduced renal mass and diabetes. J Nephrol 2006;19 [Suppl 9]: S11-S17
18. Kim YH, Kwon TH, Christensen BM et al. Altered expression of renal acid-base transporters in rats with lithium-induced NDI. Am J Physiol Renal Physiol 2003; 285 (6): F1244-F1257
19. Hakam AC, Siddiqui AH, Hussain T. Renal angiotensin II AT2 receptors promote natriuresis in streptozotocin-induced diabetic rats. Аm J Physiol Renal Physiol 2006; 290 (2): F503-F508
20. O’Neill H, Lebeck J, Collins PB. Aldosterone-mediated apical targeting of ENaC subunits is blunted in rats with streptozotocin-induced diabetes mellitus. Nephrol Dial Transplant 2007; 19 (5): 1208-1217
21. Bickel CA, Knepper MA, Verbalis JG, Ecelbarger CA. Dysregulation of renal salt and water transport proteins in diabetic Zucker rats. Kidney Int 2002; 61 (6): 2099-2110
22. Vidotti DB, Arnoni CP, Boim MA. Effect of long-term type 1 diabetes on renal sodium and water transporters in rats. Am J Nephrol 2008; 28 (1): 107-114
23. Nielsen J, Kwon TH, Praetorius J. Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus. Am J Physiol Renal Physiol 2006; 290 (2): F438-449
24. Hryciw DH, Lee EM, Pollock CA, Poronnik P. Molecular changes in proximal tubule function in diabetes mellitus. Clin Exp Pharmacol Physiol 2004; 31 (5-6): 372-379
25. Nielsen S, Marples D, Kwon TH et al. Aquaporins in the kidney: from molecules to medicine. Physiol Rev 2002; 82 (1): 205-244
26. Bedford JJ, Leader JP, Walker RJ. Aquaporin expression in normal human kidney and in renal disease. J Am Soc Nephrol 2003; 14(10): 2581-2587
27. Noda Y, Sasaki S. Regulation of aquaporin-2 trafficking and its binding protein complex. Biochim Biophys Acta 2006; 1758 (8): 1117-1125
28. RodrГ-guez-Mulero S, Errasti-Murugarren E Expression of concentrative nucleoside transporters SLC28 (CNT1, CNT2, and CNT3) along the rat nephron: effect of diabetes. Kidney Int 2005; 68 (2): 665-672
29. Marks J, Carvou NJ, Debnam ES. Diabetes increases facilitative glucose uptake and GLUT2 expression at the rat proximal tubule brush border membrane. J Physiol 2003; 553 (Pt 1): 137-145
30. Linden KC, DeHaan CL, Zhang Y et al. Renal expression and localization of the facilitative glucose transporters GLUT1 and GLUT12 in animal models of hypertension and diabetic nephropathy. Am J Physiol Renal Physiol 2006; 290 (1): F205-213
31. Vestri S, Okamoto MM, Nunes MT. Changes in sodium or glucose filtration rate modulate expression of glucose transporters in renal proximal tubular cells of rat. J Membr Biol 2001; 182 (2): 105-112
32. Katsuno K, Fujimori Y, Takemura Y. Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal glucose reabsorption and modulates plasma glucose level. J Pharmacol Exp Ther 2007; 320 (1): 323-330
33. Ueta K, Yoneda H, Oku A, Nishiyama S. Reduction of renal transport maximum for glucose by inhibition of NA(+)- glucose cotransporter suppresses blood glucose elevation in dogs. Biol Pharm Bull 2006; 29 (1): 114-118
34. Pontoglio M, PriГ© D, Cheret C et al. HNF1alpha controls renal glucose reabsorption in mouse and man. EMBO Rep 2000; 1 (4): 359-365
35. Isaji M. Sodium-glucose cotransporter inhibitors for diabetes. Curr Opin Investig Drugs2007; 8 (4): 285-292
36. Saito A, Takeda T, Hama H et al. Role of megalin, a proximal tubular endocytic receptor, in the pathogenesis of diabetic and metabolic syndrome-related nephropathies: protein metabolic overload hypothesis. Nephrology 2005; 10 Suppl: S26-S31
37. Tojo A, Onozato ML, Ha H. Reduced albumin reabsorption in the proximal tubule of early-stage diabetic rats. Histochem Cell Biol 2001; 116 (3): 269-276
38. Tojo A, Onozato ML, Kurihara H, Sakai T. Angiotensin II blockade restores albumin reabsorption in the proximal tubules of diabetic rats. Hypertens Res 2003; 26 (5): 413-419
39. Sarafidis PA, Lasaridis AN. Actions of peroxisome proliferator-activated receptors-gamma agonists explaining a possible blood pressure-lowering effect. Am J Hypertens 2006; 19 (6): 646-653
40. Castaneda F, Burse A, Boland W, Kinne RK. Thioglycosides as inhibitors of hSGLT1 and hSGLT2: potential therapeutic agents for the control of hyperglycemia in diabetes. Int J Med Sci 2007; 4 (3): 131-139
41. Kikuchi Y, Kobayashi S, Hemmi N. Galectin-3-positive cell infiltration in human diabetic nephropathy. Nephrol Dial Transplant 2004; 19 (3): 602-607
42. Karalliedde J, Buckingham RE. Thiazolidinediones and their fluid-related adverse effets: facts, fiction and putative management strategies. Drug Saf 2007; 30 (9): 741-753
43. Sarafidis PA, Nilsson PM. The effects of thiazolidinediones on blood pressure levels – a systematic review. Blood Press 2006; 15 (3): 135-150
44. Song J, Knepper MA, Hu X, Verbalis JG, Ecelbarger CA. Rosiglitazone activates renal sodium- and water-reabsorptive pathways and lowers blood pressure in normal rats. J Pharmacol Exp Ther 2004; 308 (2): 426-433
Review
For citations:
Barinov E.F., Sulaeva O.N. MOLECULAR MECHANISMS OF FUNCTIONING RENAL TUBULES IN DIABETES MELLITUS: DECISION ON A NEW STRATEGY OF PROPHYLACTICS AND TREATMENT OF DIABETIC NEPHROPATHY. Nephrology (Saint-Petersburg). 2008;12(2):29-35. (In Russ.) https://doi.org/10.24884/1561-6274-2008-12-2-29-35
Views:
396
Email this article 