Summary
The three-dimensional ultrastructure of glomerular basement membrane (GBM) and mesangial matrix (MM) at an early stage of streptozotocin (STZ)-induced diabetes mellitus in rats was examined by the quick-freezing and deep-etching method. In diabetic rats, the GBM inner layer was diffusely enlarged and the meshwork structure not only in the GBM middle layer but also in the MM became markedly irregular due to the rupture of fine fibrils. This irregularity and enlargement of the mesh pores in diabetic rats developed during the experimental period and was significantly different from results in control rats. Insulin treatment from 1 week after STZ injection had significant effects in preventing the ultrastructural changes in the GBM and MM. It is suggested that early insulin treatment has significant effects in preventing size barrier disturbance of GBM and MM in STZ-induced diabetes.
Similar content being viewed by others
Abbreviations
- GBM:
-
Glomerular basement membrane
- MM:
-
mesangial matrix
- STZ:
-
streptozotocin
- QF-DE:
-
quick-freezing and deep-etching
- LDM:
-
longest dimension of meshpores
References
Rosenstock J, Raskin P (1986) Early diabetic nephropathy: assessment and potential therapeutic interventions. Diabetes Care 9: 529–545
Boushey HA, Warnock DG, Smith LH (1986) The pathogenesis and prevention of diabetic nephropathy. West J Med 145: 222–227
The Diabetes Control and Complication Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Eng J Med 329: 977–986
Elving LD, Wetzels JFM, Vanlier HJJ, Denobel E, Berden JHM (1994) Captopril and atenolol are equally effective in retarding progression of diabetic nephropathy. Diabetologia 37: 604–609
Nielsen FS, Rossing P, Gall MA, Skott P, Smidt UM, Parving HH (1994) Impact of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy. Diabetes 43: 1108–1113
Mogensen CE, Andersen MJF (1975) Increased kidney size and glomerular filtration rate in untreated juvenile diabetes: normalization by insulin-treatment. Diabetologia 11: 221–224
Christiansen JS, Gammelgaad J, Tronier B, Svendsen PA, Parving HH (1982) Kidney function and size in diabetics before and during initial insulin treatment. Kidney Int 21: 683–688
Reyers AA, Karl IE, Kissane J, Klahr S (1993) L-arginine administration prevents glomerular hyperfiltration and decreases proteinuria in diabetic rats. J Am Soc Nephrol 4: 1039–1045
Matsubara M, Taguma Y, Kurosawa K, Hotta O, Suzuki K, Ishigaki M (1990) Effect of camostat mesilate for the treatment of advanced diabetic nephropathy. J Lab Clin Med 116: 206–210
Pasariello N, Sepe J, Marrazzo G et al. (1993) Effect of aldose reductase inhibitor (tolrestat) on urinary albumin excretion rate and glomerular filtration rate in IDDM subjects with nephropathy. Diabetes Care 16: 789–795
Mauer SM, Steffes MW, Ellis EN, Sutherland DER, Brown DM, Goetz FC (1984) Structural-functional relationships in diabetic nephropathy. J Clin Invest 97: 1143–1155
Østerby R (1988) Glomerular abnormalities in early and late stages of experimental diabetes:models for diabetic nephropathy? In: Shafrir E, Renold AE (eds) Frontiers in diabetes research. Lessons from animal diabetes, vol 2. John Libbey & Company, London, pp 522–527
Heuser JE, Kirschner MW (1980) Filament organization revealed in platinum replicas of freeze-dried cytoskeltons. J Cell Biol 86: 212–234
Ohno S (1985) Immunocytochemical study on the cytoplasmic side of cell membranes infected with vesicular stomatitis virus by quick-freezing and deep-etching replica method. Histochemistry 82: 565–575
Naramoto A, Ohno S, Itoh N et al. (1991) Ultrastructure of matriceal changes in chronic phase of Masugi nephritis by quick-freezing and deep-etching method. Virchows Arch A 418: 51–59
Naramoto A, Ohno S, Nakazawa K, Takami H, Itoh N, Shigematsu H (1991) Three-dimensional ultrastructure of glomerular injury in serum sickness nephritis using the quick-freezing and deep-etching method. Virchows Arch A 418: 185–192
Nakazawa K, Ohno S, Naramoto A et al. (1992) Immune deposits in the glomerular extracellular matrix detected by the quick-freezing and deep-etching method. Nephron 62: 203–212
Ohtani M, Ohno S, Aoki I, Misugi K, Nakazawa K, Shigematsu H (1993) Three-dimensional study of glomerular lesions in murine chronic graft-versus-host reaction by quick-freezing and deep-etching method. Nephron 64: 268–274
Kasahara H (1992) Reconstruction of glomerular tufts-observation of mesangiolysis induced by anti-thymocyte serum. Jpn J Nephrol 34: 1117–1133
Moriya T, Ohno S, Nakazawa K, Shigematsu H, Yajima Y (1993) Ultrastructural study of glomerular basement membrane in diabetic rats by quick-freezing and deep-etching method. Virchows Arch B 64: 107–114
Rasch R (1979) Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. Kidney size and glomerular volume. Diabetologia 16: 125–128
Rasch R (1979) Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. Glomerular basement menbrane thickness. Diabetologia 16: 319–324
Moriya T, Nakazawa K, Itoh N et al. (1993) Loss of glomerular anionic sites and development of albuminuria in rats with streptozotocin-induced diabetes. Nephron 65: 444–448
Latta H, Fligiel S (1985) Mesangial fenestrations, sieving, filtration, and flow. Lab Invest 52: 591–598
Xiao MH, Carter DC (1992) Atomic structure and chemistry of human serum albumin. Nature 358: 209–215
Olivetti G, Kithier K, Giacomelli F, Wiener J (1981) Glomerular permeability to endogenous proteins in the rat. Effect of acute hypertension. Lab Invest 44: 127–137
Batsford SR, Rourbach R, Vogt A (1987) Size restriction in the capillary wall: importance of lamina densa. Kidney Int 31: 710–717
Takami H, Naramoto A, Shigematsu H, Ohno S (1991) Ultrastructure of glomerular basement membrane by quick-freeze and deep-etch methods. Kidney Int 39: 659–664
Viberti GC, Wiseman MJ (1986) The kidney in diabetes: significance of the early abnormalities. Clin Endocri Metabol 15: 753–782
Ayo SH, Radnik RA, Garoni JA, Glass II WF, Kreisberg JI (1990) High glucose causes an increase in extracellular matrix proteins in cultured mesangial cells. Am J Pathol 136: 1339–1348
Haneda M, Kikkawa R, Horide N et al. (1991) Glucose enhances type IV collagen production in cultured rat glomerular mesangial cells. Diabetologia 34: 198–200
Kitamura M, Kitamura A, Mitarai T et al. (1992) Gene expression of metalloproteinase and its inhibitor in mesangial cells exposed to high glucose. Biochem Biophys Res Commun 185: 1048–1054
Kanwar YS, Rosenzweig LJ, Linker A, Jakubouski ML (1983) Decreased de novo synthesis of glomerular proteoglycans in diabetes: biochemical and autoradiographic evidence. Proc Natl Acad Sci 80: 2272–2275
Leblond CP, Inoue S (1989) Structure, composition and assembly of basement membrane. Am J Anat 185: 367–390
Tarsio JF, Reger LA, Furcht LT (1988) Molecular mechanisms in basement membrane complications of diabetes. Alterations in heparin, laminin and type IV collagen association. Diabetes 37: 532–539
Haitoglou CS, Tsilibary EC, Brownlee M, Charonis AS (1992) Altered cellular interactions between endothelial cells and nonenzymatically glycosilated laminin/type IV collagen. J Biol Chem 25: 12404–12407
Anderson SS, Tsilibary EC, Charonis AS (1993) Nonenzymatic glycosilation-induced modifications of intact bovine kidney tubular basement membrane. J Clin Invest 92: 3045–3052
Bangstad HJ, Kofoed-Enevoldsen A, Dahl-Jogensen K, Hanssen KF (1992) Glomerular charge selectivity and the influence of improved blood glucose control in type 1 (insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 35: 1165–1169
Wiegmann TB, Herron KG, Chonko AM, Macdougall ML, Moore WV (1992) Effect of angiotensin-converting enzyme inhibition on renal function and albuminuria in normotensive type I diabetic patients. Diabetes 41: 62–67
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Moriya, T., Ohno, S., Tanaka, K. et al. Effects of early insulin treatment on ultrastructural changes of glomeruli in diabetic rats revealed by the quick-freezing and deep-etching method. Diabetologia 39, 632–640 (1996). https://doi.org/10.1007/BF00418534
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF00418534