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糖尿病大鼠大脑中蛋氨酸甲基利用改变的证据。

Evidence for altered methionine methyl-group utilization in the diabetic rat's brain.

作者信息

Dyer J R, Greenwood C E

机构信息

Dept. of Nutritional Sciences, University of Toronto, Ontario, Canada.

出版信息

Neurochem Res. 1988 Jun;13(6):517-23. doi: 10.1007/BF00973290.

DOI:10.1007/BF00973290
PMID:2970016
Abstract

The methionine (MET) derivative, S-adenosylmethionine (SAM), provides methyl-groups for methylation reactions in many neural processes. In rats made diabetic with streptozotocin (SZ), brain SAM levels were generally lower (10-20%) than in controls, with a constant decrease being observed five weeks after onset of diabetes. This decrease in SAM levels may be due to reduced precursor (MET) availability because greatly elevating plasma MET concentrations in SZ diabetic rats by dietary manipulation increased their neural SAM concentrations to be approximately or even greater than (5-20%) those of controls. In contrast, neural levels of SAM's demethylated product, S-adenosylhomocysteine (SAH), were reduced to a greater extent (17-44%) than SAM levels in all groups of SZ diabetic rats independent of their plasma MET concentrations or brain SAM levels. This indicates that the decrease in SAH levels is not simply due to substrate (SAM) restriction. These changes in MET metabolites appear to be a general effect of diabetes rather than a non-pancreatic side-effect of SZ, because genetically diabetic BB Wistar rats also exhibited reduced brain SAM (25%) and brain SAH (46%) levels. These results indicate that methyl-groups from MET are handled differently in the brain of the diabetic rat, which considering the variety and importance of neural methylation reactions, could have important consequences for the diabetic.

摘要

蛋氨酸(MET)衍生物S-腺苷甲硫氨酸(SAM)为许多神经过程中的甲基化反应提供甲基基团。在用链脲佐菌素(SZ)诱导糖尿病的大鼠中,脑内SAM水平通常比对照组低(10 - 20%),糖尿病发病五周后可观察到其持续下降。SAM水平的这种下降可能是由于前体(MET)可用性降低,因为通过饮食控制大幅提高SZ糖尿病大鼠的血浆MET浓度可使它们神经中的SAM浓度达到约等于甚至高于(5 - 20%)对照组的水平。相比之下,在所有SZ糖尿病大鼠组中,无论其血浆MET浓度或脑内SAM水平如何,SAM的去甲基化产物S-腺苷同型半胱氨酸(SAH)的神经水平比SAM水平降低的程度更大(17 - 44%)。这表明SAH水平的降低并非仅仅由于底物(SAM)受限。MET代谢产物的这些变化似乎是糖尿病的普遍效应,而非SZ的非胰腺副作用,因为遗传性糖尿病BB Wistar大鼠也表现出脑内SAM水平降低(25%)和脑内SAH水平降低(46%)。这些结果表明,在糖尿病大鼠脑中,来自MET的甲基基团的处理方式有所不同,鉴于神经甲基化反应的多样性和重要性,这可能对糖尿病患者产生重要影响。

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J Neurochem. 1982 Mar;38(3):810-5. doi: 10.1111/j.1471-4159.1982.tb08702.x.
2
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Am J Clin Nutr. 1981 May;34(5):914-23. doi: 10.1093/ajcn/34.5.914.
3
Spontaneous autoimmune diabetes mellitus in the BB rat.BB大鼠自发性自身免疫性糖尿病
Diabetes. 1982;31(Suppl 1 Pt 2):7-13. doi: 10.2337/diab.31.1.s7.
4
Metabolic fuel and amino acid transport into the brain in experimental diabetes mellitus.实验性糖尿病中代谢燃料和氨基酸向大脑的转运
Proc Natl Acad Sci U S A. 1982 Sep;79(17):5406-10. doi: 10.1073/pnas.79.17.5406.
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Carnitine and creatine content of tissues of normal and alloxan-diabetic sheep and rats.正常及四氧嘧啶糖尿病绵羊和大鼠组织中的肉碱和肌酸含量
Comp Biochem Physiol B. 1983;76(2):295-8. doi: 10.1016/0305-0491(83)90073-1.
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