Effects of Vitamin E Supplementation on Renal Glycosylation Products in Diabetic KK Mice

당뇨 KK마우스에서 비타민 E 보강식이가 신장 당화단백질 생성에 미치는 영향

  • 안현숙 (서울대학교 식품영양학과) ;
  • 박성연 (서울대학교 식품영양학과) ;
  • 김해리 (서울대학교 식품영양학과)
  • Published : 1998.07.01

Abstract

We investigated the effects of vitamin E supplementation on protein glycosylation in early and end stage product, and light microscopic studies were done on the renal glomeruli of KK-mice of various ages and various duration of diabetes. Weaned KK-mice were fed high fat diets containing 20% corn oil(wt/wt), and sacrificed at 4,6, and 9 months of age. The high vitamin E diet was a high fit diet supplemented with an excess amount of d1-$\alpha$-tocopheryl acetate (2080IU/kg diet). We measured Hemoglobin $A_{IC}$ (Hb $A_{IC}$) as a glycosylation early product, and renal collagen-linked fluorescence as a glycosylation end product. In the diabetic group, levels of Hb $A_{IC}$ were increased within 2 months after onset of diabetes and remained at a constant level for the duration of experiment. 5 months after onset of diabetes, renal collagen linked fluorescence(CLF) was markedly increased. A quantative, morphologically demonstratable, progressive thickening of the basement membrane and calcification occured in the diabetic KK-mice. There is a statiscally positive correlation between CLF and histologic grade of diabetic nephropathy. Hepatic vitamin E levels correlated with those of Hb $A_{IC}$, renal CLF, and renal calcification. Treatment with vitamin I did not modify the level of blood glucose. However, we observered a significant lowering of CLF and Hb $A_{IC}$ in diabetic mice. Supplementation of vitamin E was found to delay the progression of diabetic nephropathy. (forean J Nutrition 31(6) : 1024-1030, 1998)0, 1998)

KK마우스에 고지방 식이를 섭취시켜 당뇨를 유발하고, Maillard 반응의 초기산물인 Hb $A_{IC}$와 후기 산물인 신장조직의 CLF가 증가되는지를 확인하고. 당뇨병에 의해 증가되는 Maillard 반응이 비타민 I의 투여로 억제되는지 관찰하였다. 또 신장조직의 광학 현미경 관찰을 통하여 신장병변을 검사하였다. 이유즉시 KK마우스를 1개월간 pellet diet로 적응시킨 후 저비타민 E 식이(corn oil 20%, wt/wt)를 먹여 당뇨를 유도하였다. 비타민 E 보강은 2080IU/kg diet 수준으로 하였으며. 생후 4개월 , 6개월 . 9개월(당뇨 0개월. 2개월, 5개월)에 희생시켰다. 정상 KK-마우스에서는 월령이 증가하였을 때. 혈당과 Hb $A_{IC}$는 유의적인 변화를 보이지 않았으나 신장조직의 CLF는 점진적으로 증가되었다. 당뇨군에서 Hb $A_{IC}$는 6개월에서 증가되기 시작하였고 9개월군과 차이가 없었으며 . 신장조직의 CLF는 9개월 군에서 급격히 증가하였다. 또 고비타민 E 식이를 섭취시킨 경우 당뇨군에서 초기 및 후기 Maillard 반응생성물의 감소가 관찰되었다. 이상의 결과로부터 KK마우스에서는 월령이 증가함에 따라 초기 및 후기 당화산물의 축적과 신장 병변의 변화가 관찰되었고, 또한 당뇨 유발에 의해 이 변화들은 더욱 촉진되었으나, 2080IU/kg diet 수준의 고비타민 E 식이를 섭취시켰을 때 이런 변들이 억제되었음을 확인하였다.확인하였다.

Keywords

References

  1. Annu Rev Med v.46 Advanced protein glycosylation in diabetes and aging Brownlee,M.
  2. Proc Nat Acad Sci USA v.88 Aminoguanidine treatment inhibit the development of experimental diabetic retinopathy Hammes,H.D.;Martin,S.;Fedesrlin,K.;Geisen,K.Brownlee,M.
  3. Diabetes v.42 Immunochemical detection of advanced glycation end product in lens crystallins from streptozotocin-induced diabetic rat Nakayama,H.;Mitsuhashi,T.;Kuwajimas
  4. N Engl J Med v.318 Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications Brownlee,M.;Cerami,A.;Vassara,H.
  5. Diabetic Med v.9 New insights on non-enzymatic glycosylation may lead to therapeutic approaches for the prevention of diabetic complications Ceriello,A.;Quatraro,A.;Gingliano,D.
  6. Diabetes care v.14 Vitamin E reduction of protein glycosylation in diabetes Ceriello,A.;Giugliano,D.;Quatraro,A.;Donzella,C.;Dipalo,G.;Lefevre,P.J.
  7. Lab Invest v.60 Advanced glycosylation end-products in experimental murine diabetic nephropathy. Effect of islet isografting and of aminoguanidine Nicholls,K.;Mandel,T.E.
  8. Am J Clin Nutr v.57 Pharmacological doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetes patients Paolisso,G.;D'Amore,A.
  9. Acta Med Scand v.574 no.Suppl Early phases in the development of diabetic glomerulopathy Osterby,R.
  10. Ann Intern Med v.101 Nonenzymatic glycosylation and the pathongenesis of diabetic complications Brownlee,M.;Vlassara,H.;Cerami,A.
  11. Diabetologia Diabetes in the KK-mouse Dulin,W.E.;Wyse,B.M.
  12. Lab Invest v.27 no.3 Glomerular changes in mice with spontaneous hereditary diabetes Wehner,H.;Hohn,D.;Faix-Schade,U.;Huber,H.;Wazlser,P.
  13. Clincal Pathology File Yi,K.N.;Rhee,C.S.
  14. Diabetes v.40 Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozotocin-induced diabetic rat Soulis-Liparota,T.;Cooper,M.;Papazoglou,D.;Clarke,B.;Jerums,G.
  15. Anal Biochem v.150 Measurement of protein using bicinchonic acid Smith,P.K.;Krohn,R.I.;Hermanson,G.T.;Mallia,A.K.;Gartner,F.H.;Drovenzano,M.D.;Fujimoto,E.K.;Goeke,N.M.;Olson,B.J.;Klenk,D.C.
  16. J Chromatogr v.309 Gradient reversed-phased high-performance liquid chromatographic separation of naturally occuring retinoids Furr,H.C.;Amedee-Maneseme,O.;Olson,J.A.
  17. Diabetologia v.18 Fast accumulation of basement membrane material and the rate of morphological changes in acute experimental diabetic glomerular hypertrophy Osterby,R.;Gundersen,H.J.G.
  18. Horm Metabol Res v.14 Determination of overall insulin sensitivity in diabetic mice KK Taketomi,S.;Ikeda,H.;Iwatsuka,H.
  19. Diabetologia v.6 Studies of vascular and other lesions in KK mice Camerini-Davalos,R.A.;Oppermann,W.;Mittl,R.;Ehrenerigh,T.
  20. Am J Clin Nutr v.37 Vitamin E in plasma and platelets of human diabetic patients and control subjects Vatassery,G.T.;Morley,J.E.;Kuskowski,M.A.
  21. Horm Met Res v.14 The effect of diabetes on the activities of the peroxide metabolizing enzymes Matkovices,B.;Barage,S.I.;Szabo,L.;Witas,H.
  22. Acta Med Okayama v.36 no.3 Lipid peroxides and α-tocopherol in rat streptozotocin-induced diabetes mellitus Higuchi,Y.
  23. The red blood cell Ⅱ The biological life of the red cell Berlin,N.;Berk,P.;Surgenor,D.M.(ed.)
  24. J Mol Biol v.181 Neutron diffraction studies of collagen in fully mineralized bone Bonar,L.C.;Lees,S.;Mook,H.A.
  25. Clinical Pharmacology in the Elderly Normal aging and its parameters Kohn,R.R.;Monnier,V.M.;Swift,C.G.(ed.)
  26. Proc Natl Acad Sci U.S.A. v.81 Accelerated age related browning of human collagen in diabetes mellitus Monnier,V.M.;Kohn,R.R.;Cerami,A.
  27. Biochem J v.256 Hydroxyl radical production and antioxidative glycosylation Hunt,J.V.;Dean,R.T.;Wolff,S.P.
  28. Biochem Pharmacol v.46 Aminoguanidine : A drug proposed for prophylaxis in diabetes inhibits catalase and generates hydrogen peroxide in vitro Ou,P.;Wolff,S.
  29. Diabetes v.39 Prevention of diabetes-increased aging effect on rat collagen-linked fluorescence by aminoguanidine and rutin Odetti,P.R.;Borgrglio,A.;Pascal,A.D.Rolandi,R.;Adezati,L.