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Gene Review

Akr1b1  -  aldo-keto reductase family 1, member B1...

Rattus norvegicus

Synonyms: ALDRED, ALR-P-I, AR, Akr1b3, Akr1b4, ...
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Disease relevance of Akr1b4


Psychiatry related information on Akr1b4


High impact information on Akr1b4


Chemical compound and disease context of Akr1b4


Biological context of Akr1b4


Anatomical context of Akr1b4


Associations of Akr1b4 with chemical compounds


Physical interactions of Akr1b4


Regulatory relationships of Akr1b4


Other interactions of Akr1b4

  • This study demonstrates AR and SDH in substructures of the kidney [19].
  • We examined the contribution of aldose reductase, which catalyzes the first, and the rate-limiting, step of the polyol pathway of glucose metabolism, to PKC activation in vascular smooth muscle cells (VSMCs) isolated from rat aorta and exposed to high glucose in culture [21].
  • Inhibition of aldose reductase prevented membrane translocation of PKC-beta2 and -delta and delayed the activation of PKC-beta1 and -epsilon, whereas membrane translocation of PKC-alpha and -gamma was not affected [21].
  • Biochemically, there was elevation of gamma-glutamyl transferase, a decrease in sorbitol levels at 3 h and a decrease in the activity of aldose reductase at 6 h, in the testes of treated rats [23].
  • Insulin and aldose reductase inhibitors can prevent excess polyol pathway flux, and hence these agents may prevent NCV deficits by preventing p38 MAP kinase activation [24].

Analytical, diagnostic and therapeutic context of Akr1b4

  • Nonradioactive in situ hybridization studies on sections from formalin-fixed and paraffin-embedded, normally concentrating kidneys showed strong expression of BGT, SMIT, and AR mRNAs in interstitial and collecting duct cells of the papilla, whereas expression of SDH mRNA was much weaker in both cell types [25].
  • The enzymatic activities, expression, and localization of AR and SDH were studied in reproductive tracts and spermatozoa of male rats by immunohistochemistry, Western blotting, and enzyme assays [26].
  • Second, in rats fed a low-protein diet for 3 wk, aldose reductase mRNA increased two-fold, whereas sorbitol dehydrogenase and taurine cotransporter mRNA were unchanged [6].
  • Oral administration of tolrestat, a structurally novel aldose reductase inhibitor (n = 8; 20 mg/kg twice daily 1 wk before and 4 wk after STZ injection), prevented the diabetes-induced increase in distal nerve transmission time [27].
  • Both rat and human retinal endothelial cells showed aldose reductase immunoreactivity, and human retinas exposed to high glucose in organ culture increased the production of sorbitol by a degree similar to that observed in the rat [28].


  1. Analysis of gene expression of aldose reductase and sorbitol dehydrogenase in rat Schwann cells by competitive RT-PCR method using non-homologous DNA standards. Maekawa, K., Tanimoto, T., Okada, S., Suzuki, T., Suzuki, T., Yabe-Nishimura, C. Brain Res. Brain Res. Protoc. (2001) [Pubmed]
  2. Biochemical and morphological changes during development of sugar cataract in Otsuka Long-Evans Tokushima fatty (OLETF) rat. Kubo, E., Maekawa, K., Tanimoto, T., Fujisawa, S., Akagi, Y. Exp. Eye Res. (2001) [Pubmed]
  3. Aldose reductase activation is a key component of myocardial response to ischemia. Hwang, Y.C., Sato, S., Tsai, J.Y., Yan, S., Bakr, S., Zhang, H., Oates, P.J., Ramasamy, R. FASEB J. (2002) [Pubmed]
  4. Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats. Cameron, N.E., Cotter, M.A., Basso, M., Hohman, T.C. Diabetologia (1997) [Pubmed]
  5. Effect of sorbitol dehydrogenase inhibition on experimental diabetic autonomic neuropathy. Schmidt, R.E., Dorsey, D.A., Beaudet, L.N., Plurad, S.B., Williamson, J.R., Ido, Y. J. Neuropathol. Exp. Neurol. (1998) [Pubmed]
  6. Regulation of aldose reductase, sorbitol dehydrogenase, and taurine cotransporter mRNA in rat medulla. Martial, S., Price, S.R., Sands, J.M. J. Am. Soc. Nephrol. (1995) [Pubmed]
  7. The antiestrogen ICI 182,780 decreases the expression of estrogen receptor-alpha but has no effect on estrogen receptor-beta and androgen receptor in rat efferent ductules. Oliveira, C.A., Nie, R., Carnes, K., Franca, L.R., Prins, G.S., Saunders, P.T., Hess, R.A. Reprod. Biol. Endocrinol. (2003) [Pubmed]
  8. Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications. Greene, D.A., Lattimer, S.A., Sima, A.A. N. Engl. J. Med. (1987) [Pubmed]
  9. Retinal dystrophy: development retarded by galactose feeding in spontaneously hypertensive rats. Frank, R.N., Keirn, R.J., Keirn, G.V., Mancini, M.A., Khoury, J.K. Science (1986) [Pubmed]
  10. Retinal capillaries: basement membrane thickening by galactosemia prevented with aldose reductase inhibitor. Robison, W.G., Kador, P.F., Kinoshita, J.H. Science (1983) [Pubmed]
  11. Long-term induction of an aldose reductase protein by basic fibroblast growth factor in rat astrocytes in vitro. Laeng, P., Bouillon, P., Taupenot, L., Labourdette, G. Electrophoresis (1995) [Pubmed]
  12. The linked roles of nitric oxide, aldose reductase and, (Na+,K+)-ATPase in the slowing of nerve conduction in the streptozotocin diabetic rat. Stevens, M.J., Dananberg, J., Feldman, E.L., Lattimer, S.A., Kamijo, M., Thomas, T.P., Shindo, H., Sima, A.A., Greene, D.A. J. Clin. Invest. (1994) [Pubmed]
  13. NIH conference. Aldose reductase and complications of diabetes. Cogan, D.G., Kinoshita, J.H., Kador, P.F., Robison, G., Datilis, M.B., Cobo, L.M., Kupfer, C. Ann. Intern. Med. (1984) [Pubmed]
  14. Myocardial protection by brief ischemia in noncardiac tissue. Gho, B.C., Schoemaker, R.G., van den Doel, M.A., Duncker, D.J., Verdouw, P.D. Circulation (1996) [Pubmed]
  15. Aldose reductase induced by hyperosmotic stress mediates cardiomyocyte apoptosis: differential effects of sorbitol and mannitol. Galvez, A.S., Ulloa, J.A., Chiong, M., Criollo, A., Eisner, V., Barros, L.F., Lavandero, S. J. Biol. Chem. (2003) [Pubmed]
  16. Aldose reductase mediates mitogenic signaling in vascular smooth muscle cells. Ramana, K.V., Chandra, D., Srivastava, S., Bhatnagar, A., Aggarwal, B.B., Srivastava, S.K. J. Biol. Chem. (2002) [Pubmed]
  17. Characterization of the aldose reductase-encoding gene family in rat. Graham, C., Szpirer, C., Levan, G., Carper, D. Gene (1991) [Pubmed]
  18. Sorbitol dehydrogenase overexpression potentiates glucose toxicity to cultured retinal pericytes. Amano, S., Yamagishi, S., Kato, N., Inagaki, Y., Okamoto, T., Makino, M., Taniko, K., Hirooka, H., Jomori, T., Takeuchi, M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  19. Aldose reductase and sorbitol dehydrogenase distribution in rat kidney. Corder, C.N., Collins, J.G., Brannan, T.S., Sharma, J. J. Histochem. Cytochem. (1977) [Pubmed]
  20. Studies of sorbinil on axonal transport in streptozotocin-diabetic rats. Willars, G.B., Tomlinson, D.R., Robinson, J.P. Metab. Clin. Exp. (1986) [Pubmed]
  21. Requirement of aldose reductase for the hyperglycemic activation of protein kinase C and formation of diacylglycerol in vascular smooth muscle cells. Ramana, K.V., Friedrich, B., Tammali, R., West, M.B., Bhatnagar, A., Srivastava, S.K. Diabetes (2005) [Pubmed]
  22. High glucose augments the angiotensin II-induced activation of JAK2 in vascular smooth muscle cells via the polyol pathway. Shaw, S., Wang, X., Redd, H., Alexander, G.D., Isales, C.M., Marrero, M.B. J. Biol. Chem. (2003) [Pubmed]
  23. Mechanism of testicular atrophy induced by di-n-butyl phthalate in rats. Part 2. The effects on some testicular enzymes. Fukuoka, M., Zhou, Y., Tanaka, A., Ikemoto, I., Machida, T. Journal of applied toxicology : JAT. (1990) [Pubmed]
  24. Mitogen-activated protein kinase p38 mediates reduced nerve conduction velocity in experimental diabetic neuropathy: interactions with aldose reductase. Price, S.A., Agthong, S., Middlemas, A.B., Tomlinson, D.R. Diabetes (2004) [Pubmed]
  25. Hypertonicity-induced accumulation of organic osmolytes in papillary interstitial cells. Burger-Kentischer, A., Müller, E., März, J., Fraek, M.L., Thurau, K., Beck, F.X. Kidney Int. (1999) [Pubmed]
  26. Localization and physiological implication of aldose reductase and sorbitol dehydrogenase in reproductive tracts and spermatozoa of male rats. Kobayashi, T., Kaneko, T., Iuchi, Y., Matsuki, S., Takahashi, M., Sasagawa, I., Nakada, T., Fujii, J. J. Androl. (2002) [Pubmed]
  27. Tolrestat, an aldose reductase inhibitor, prevents nerve dysfunction in conscious diabetic rats. Notvest, R.R., Inserra, J.J. Diabetes (1987) [Pubmed]
  28. Studies of rat and human retinas predict a role for the polyol pathway in human diabetic retinopathy. Dagher, Z., Park, Y.S., Asnaghi, V., Hoehn, T., Gerhardinger, C., Lorenzi, M. Diabetes (2004) [Pubmed]
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