Anatomy and Cell Biology

Korean Association of Anatomists (대한해부학회)
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Psammomys obesus, a particularly important animal model for the study of the human diabetic nephropathy

  • Scherzer, Pnina (Nephrology and Hypertension Unit, Hadassah University Hospital) ;
  • Katalan, Shachaf (Nephrology and Hypertension Unit, Hadassah University Hospital) ;
  • Got, Gay (Nephrology and Hypertension Unit, Hadassah University Hospital) ;
  • Pizov, Galina (Department of Pathology, Hadassah University Hospital) ;
  • Londono, Irene (Department of Pathology and Cell Biology, Montreal Diabetes Center, University of Montreal) ;
  • Gal-Moscovici, Anca (Nephrology and Hypertension Unit, Hadassah University Hospital) ;
  • Popovtzer, Mordecai M. (Southern Arizona VA Health Care System) ;
  • Ziv, Ehud (Diabetes Unit, Hadassah University Hospital) ;
  • Bendayan, Moise (Department of Pathology and Cell Biology, Montreal Diabetes Center, University of Montreal)
  • Published : 2011.09.30
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Abstract

The Psammomys obesus lives in natural desert habitat on low energy (LE) diet, however when maintained in laboratory conditions with high energy (HE) diet it exhibits pathological metabolic changes resembling those of type 2 diabetes. We have evaluated and correlated the histopathology, metabolic and functional renal alterations occurring in the diabetic Psammomys. Renal function determined by measuring glomerular filtration rate (GFR), protein excretion, protein/creatinine ratio and morpho-immunocytochemical evaluations were performed on HE diet diabetic animals and compared to LE diet control animals. The diabetic animals present a 54% increase in GFR after one month of hyperglycemic condition and a decrease of 47% from baseline values after 4 months. Protein excretion in diabetic animals was 5 folds increased after 4 months. Light microscopy showed an increase in glomeruli size in the diabetic Psammomys, and electron microscopy and immunocytochemical quantitative evaluations revealed accumulation of basement membrane material as well as frequent splitting of the glomerular basement membrane. In addition, glycogen-filled Armanni-Ebstein clear cells were found in the distal tubules including the thick ascending limbs of the diabetic animals. These renal complications in the Psammomys, including changes in GFR with massive proteinuria sustained by physiological and histopathological changes, are very similar to the diabetic nephropathy in human. The Psamommys obesus represents therefore a reliable animal model of diabetic nephropathy.

Keywords

References

  1. Ritz E, Orth SR. Nephropathy in patients with type 2 diabetes mellitus. N Engl J Med 1999;341:1127-33. https://doi.org/10.1056/NEJM199910073411506
  2. Schena FP, Gesualdo L. Pathogenetic mechanisms of diabetic nephropathy. J Am Soc Nephrol 2005;16 Suppl 1:S30-3. https://doi.org/10.1681/ASN.2004110970
  3. Rudberg S, Osterby R. Decreasing glomerular filtration rate: an indicator of more advanced diabetic glomerulopathy in the early course of microalbuminuria in IDDM adolescents? Nephrol Dial Transplant 1997;12:1149-54. https://doi.org/10.1093/ndt/12.6.1149
  4. Mogensen CE. Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes. J Intern Med 2003;254:45-66. https://doi.org/10.1046/j.1365-2796.2003.01157.x
  5. Breyer MD, Bottinger E, Brosius FC 3rd, Coffman TM, Harris RC, Heilig CW, Sharma K; AMDCC. Mouse models of diabetic nephropathy. J Am Soc Nephrol 2005;16:27-45. https://doi.org/10.1681/ASN.2004110967
  6. Katoh M, Ohmachi Y, Kurosawa Y, Yoneda H, Tanaka N, Narita H. Effects of imidapril and captopril on streptozotocin-induced diabetic nephropathy in mice. Eur J Pharmacol 2000;398:381-7. https://doi.org/10.1016/S0014-2999(00)00320-4
  7. Lee SM, Bressler R. Prevention of diabetic nephropathy by diet control in the db/db mouse. Diabetes 1981;30:106-11. https://doi.org/10.2337/diabetes.30.2.106
  8. Wald H, Scherzer P, Rasch R, Popovtzer MM. Renal tubular Na(+)-K(+)-ATPase in diabetes mellitus: relationship to metabolic abnormality. Am J Physiol 1993;265(1 Pt 1):E96-101.
  9. Weksler-Zangen S, Yagil C, Zangen DH, Ornoy A, Jacob HJ, Yagil Y. The newly inbred cohen diabetic rat: a nonobese normolipidemic genetic model of diet-induced type 2 diabetes expressing sex differences. Diabetes 2001;50:2521-9. https://doi.org/10.2337/diabetes.50.11.2521
  10. Sharma K, McCue P, Dunn SR. Diabetic kidney disease in the db/db mouse. Am J Physiol Renal Physiol 2003;284:F1138-44. https://doi.org/10.1152/ajprenal.00315.2002
  11. Kalman R, Adler JH, Lazarovici G, Bar-On H, Ziv E. The efficiency of sand rat metabolism is responsible for development of obesity and diabetes. J Basic Clin Physiol Pharmacol 1993;4:57-68.
  12. Swinburn BA, Boyce VL, Bergman RN, Howard BV, Bogardus C. Deterioration in carbohydrate metabolism and lipoprotein changes induced by modern, high fat diet in Pima Indians and Caucasians. J Clin Endocrinol Metab 1991;73:156-65. https://doi.org/10.1210/jcem-73-1-156
  13. Shafrir E, Ziv E, Kalman R. Nutritionally induced diabetes in desert rodents as models of type 2 diabetes: Acomys cahirinus (spiny mice) and Psammomys obesus (desert gerbil). ILAR J 2006;47:212-24. https://doi.org/10.1093/ilar.47.3.212
  14. Scherzer P, Nachliel I, Bar-On H, Popovtzer MM, Ziv E. Renal Na-K-ATPase hyperactivity in diabetic Psammomys obesus is related to glomerular hyperfiltration but is insulin-independent. J Endocrinol 2000;167:347-54. https://doi.org/10.1677/joe.0.1670347
  15. Silva FG. Diabetic nephropathy. In: D'Agati VD, Jennette JC, Silva FG, editors. Non-neoplastic Kidney Diseases. Washington, DC: American Registry of Pathology; 2005. p.457-9.
  16. Holck P, Rasch R. Structure and segmental localization of glycogen in the diabetic rat kidney. Diabetes 1993;42:891-900. https://doi.org/10.2337/diabetes.42.6.891
  17. Robbins SL, Tucker AW Jr. The cause of death in diabetes: a report of 307 autopsied cases. N Engl J Med 1944;231:865-8. https://doi.org/10.1056/NEJM194412282312601
  18. Bendayan M. Colloidal gold post-embedding immunocytochemistry. Prog Histochem Cytochem 1995;29:1-159.
  19. Bendayan M, Gingras D, Charest P. Distribution of endogenous albumin in the glomerular wall of streptozotocin-induced diabetic rats as revealed by high-resolution immunocytochemistry. Diabetologia 1986;29:868-75. https://doi.org/10.1007/BF00870142
  20. Godfrey K. Statistics in practice. Comparing the means of several groups. N Engl J Med 1985;313:1450-6. https://doi.org/10.1056/NEJM198512053132305
  21. Danda RS, Habiba NM, Rincon-Choles H, Bhandari BK, Barnes JL, Abboud HE, Pergola PE. Kidney involvement in a nongenetic rat model of type 2 diabetes. Kidney Int 2005;68:2562-71. https://doi.org/10.1111/j.1523-1755.2005.00727.x
  22. Janssen U, Phillips AO, Floege J. Rodent models of nephropathy associated with type II diabetes. J Nephrol 1999;12:159-72.
  23. Yagil C, Barak A, Ben-Dor D, Rosenmann E, Bernheim J, Rosner M, Segev Y, Weksler-Zangen S, Raz I, Yagil Y. Nonproteinuric diabetes-associated nephropathy in the Cohen rat model of type 2 diabetes. Diabetes 2005;54:1487-96. https://doi.org/10.2337/diabetes.54.5.1487
  24. Lawson ML, Sochett EB, Chait PG, Balfe JW, Daneman D. Effect of puberty on markers of glomerular hypertrophy and hypertension in IDDM. Diabetes 1996;45:51-5. https://doi.org/10.2337/diabetes.45.1.51
  25. Wald H, Popovtzer MM. The effect of streptozotocin-induced diabetes mellitus on urinary excretion of sodium and renal Na+-K+-ATPase activity. Pflugers Arch 1984;401:97-100. https://doi.org/10.1007/BF00581539
  26. Thomson SC, Vallon V, Blantz RC. Kidney function in early diabetes: the tubular hypothesis of glomerular filtration. Am J Physiol Renal Physiol 2004;286:F8-15. https://doi.org/10.1152/ajprenal.00208.2003
  27. Vallon V, Blantz RC, Thomson S. Homeostatic efficiency of tubuloglomerular feedback is reduced in established diabetes mellitus in rats. Am J Physiol 1995;269(6 Pt 2):F876-83.
  28. Popovtzer MM. Tubular glomerular balance in diabetes mellitus. In: Shafrir E, Renold AE, editors. Lessons from animal diabetes. London/Paris: John Libbey; 1984. p.513-7.
  29. Popovtzer MM, Wald H, Scherzer P. The diabetic kidney: lesson in the resetting of tubuloglomerular feedback. In: Zhang J, Du X, Liu Z, Li H, editors. Proceedings of the 4th Asian-Pacific Congress in Nephrology. Beijing: International Academic Publishers; 1991. p.379-82.
  30. Scherzer P, Popovtzer MM. Segmental localization of mRNAs encoding Na(+)-K(+)-ATPase alpha(1)- and beta(1)-subunits in diabetic rat kidneys using RT-PCR. Am J Physiol Renal Physiol 2002;282:F492-500. https://doi.org/10.1152/ajprenal.00053.2001
  31. Velasquez MT, Michaelis OE, Szallasi T, Abraham AA, Kimmel PL, Bosch JP. Glomerular hypertrophy and mesangial expansion in the SHR/N-cp rat with type II diabetes: role of type of carbohydrate diet. Kidney Int 1990;37:523.
  32. Vora JP, Zimsen SM, Houghton DC, Anderson S. Evolution of metabolic and renal changes in the ZDF/Drt-fa rat model of type II diabetes. J Am Soc Nephrol 1996;7:113-7.
  33. Finlayson JS, Asofsky R, Potter M, Runner CC. Major urinary protein complex of normal mice: origin. Science 1965;149:981-2. https://doi.org/10.1126/science.149.3687.981
  34. Fukuzawa Y, Watanabe Y, Inaguma D, Hotta N. Evaluation of glomerular lesion and abnormal urinary findings in OLETF rats resulting from a long-term diabetic state. J Lab Clin Med 1996;128:568-78. https://doi.org/10.1016/S0022-2143(96)90129-8
  35. Myers BD, Nelson RG, Williams GW, Bennett PH, Hardy SA, Berg RL, Loon N, Knowler WC, Mitch WE. Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset. J Clin Invest 1991;88:524-30. https://doi.org/10.1172/JCI115335
  36. Andersen S, Blouch K, Bialek J, Deckert M, Parving HH, Myers BD. Glomerular permselectivity in early stages of overt diabetic nephropathy. Kidney Int 2000;58:2129-37. https://doi.org/10.1111/j.1523-1755.2000.00386.x
  37. Gall MA, Rossing P, Kofoed-Enevoldsen A, Nielsen FS, Parving HH. Glomerular size- and charge selectivity in type 2 (noninsulin-dependent) diabetic patients with diabetic nephropathy. Diabetologia 1994;37:195-201. https://doi.org/10.1007/s001250050093
  38. Rasch R. Tubular lesions in streptozotocin-diabetic rats. Diabetologia 1984;27:32-7.
  39. Rasch R, GOtzsche O. Regression of glycogen nephrosis in experimental diabetes after pancreatic islet transplantation. APMIS 1988;96:749-54. https://doi.org/10.1111/j.1699-0463.1988.tb00940.x
  40. 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;102:619-24. https://doi.org/10.1172/JCI2415
  41. Bamri-Ezzine S, Ao ZJ, Londono I, Gingras D, Bendayan M. Apoptosis of tubular epithelial cells in glycogen nephrosis during diabetes. Lab Invest 2003;83:1069-80. https://doi.org/10.1097/01.LAB.0000078687.21634.69
  42. Hennigar RA, Mayfield RK, Harvey JN, Ge ZH, Sens DA. Lectin detection of renal glycogen in rats with short-term streptozotocin-diabetes. Diabetologia 1987;30:804-11.
  43. Londono I, Bamri-Ezzine S, Gingras D, Bendayan M. Redistribution of integrins in tubular epithelial cells during diabetic glycogen nephrosis. Nephron Exp Nephrol 2004;98:e22-30. https://doi.org/10.1159/000079929
  44. Nannipieri M, Lanfranchi A, Santerini D, Catalano C, Van de Werve G, Ferrannini E. Influence of long-term diabetes on renal glycogen metabolism in the rat. Nephron 2001;87:50-7. https://doi.org/10.1159/000045884
  45. Tsuchitani M, Kuroda J, Nagatani M, Miura K, Katoh T, Saegusa T, Narama I, Itakura C. Glycogen accumulation in the renal tubular cells of spontaneously occurring diabetic WBN/Kob rats. J Comp Pathol 1990;102:179-90. https://doi.org/10.1016/S0021-9975(08)80123-5
  46. Chen YT, Coleman RA, Scheinman JI, Kolbeck PC, Sidbury JB. Renal disease in type I glycogen storage disease. N Engl J Med 1988;318:7-11. https://doi.org/10.1056/NEJM198801073180102
  47. Reitsma-Bierens WC, Smit GP, Troelstra JA. Renal function and kidney size in glycogen storage disease type I. Pediatr Nephrol 1992;6:236-8. https://doi.org/10.1007/BF00878355
  48. Verani R, Bernstein J. Renal glomerular and tubular abnormalities in glycogen storage disease type I. Arch Pathol Lab Med 1988;112:271-4.

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