DECREASE IN SKIN COLLAGEN GLYCATION WITH IMPROVED GLYCEMIC CONTROL IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS
DECREASE IN SKIN COLLAGEN GLYCATION WITH IMPROVED GLYCEMIC CONTROL IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS
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DOI：
10.1172/jci115216
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发表时间：
1991-06-01
影响因子：
15.9
通讯作者：
BAYNES, JW
中科院分区：
文献类型：
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作者：
LYONS, TJ;BAILIE, KE;BAYNES, JW
蛋白质的糖化、氧化和非酶促布朗宁都与糖尿病并发症的发生有关。蛋白质糖化的初始产物果糖赖氨酸（FL）经历进一步反应，产生复杂的布朗宁产物混合物，包括荧光赖氨酸-精氨酸交联物戊糖苷。或者，FL可被氧化裂解以形成N-α-（羧甲基）赖氨酸（CML），而糖化羟赖氨酸（胶原蛋白特有的氨基酸）可产生N-α-（羧甲基）羟赖氨酸（CMhL）。我们测量了FL，戊糖，荧光（激发= 328 nm，发射= 378 nm），CML，CMhL不溶性皮肤胶原蛋白从14名胰岛素依赖型糖尿病患者之前和之后的4个月期间的强化治疗，以改善血糖控制。平均家庭血糖从8.7 +/- 2.5（平均+/- 1 SD）降至6.8 +/- 1.4 mM（P < 0.005），平均糖化血红蛋白（HbA 1）从11.6 +/- 2.3%降至8.3 +/- 1.1%（P < 0.001）。这些变化伴随着皮肤胶原蛋白糖化的显著降低，从13.2 +/- 4.3至10.6 +/- 2.3 mmol FL/mol赖氨酸（P < 0.002）。然而，布朗宁和氧化产物（戊糖苷、CML和CMhL）和荧光水平没有变化。这些结果表明，通过改善血糖控制可以降低长寿命蛋白质的糖化，但表明一旦发生布朗宁和氧化反应对胶原蛋白的累积损伤，可能不容易逆转。因此，在糖尿病患者中，在任何时候建立和维持良好的血糖控制可能会限制糖基化和氧化反应对蛋白质的后续长期损伤程度。
Glycation, oxidation, and nonenzymatic browning of protein have all been implicated in the development of diabetic complications. The initial product of glycation of protein, fructoselysine (FL), undergoes further reactions, yielding a complex mixture of browning products, including the fluorescent lysine-arginine cross-link, pentosidine. Alternatively, FL may be cleaved oxidatively to form N-epsilon-(carboxymethyl)lysine (CML), while glycated hydroxylysine, an amino-acid unique to collagen, may yield N-epsilon-(carboxymethyl)hydroxylysine (CMhL). We have measured FL, pentosidine, fluorescence (excitation = 328 nm, emission = 378 nm), CML, and CMhL in insoluble skin collagen from 14 insulin-dependent diabetic patients before and after a 4-mo period of intensive therapy to improve glycemic control. Mean home blood glucose fell from 8.7 +/- 2.5 (mean +/- 1 SD) to 6.8 +/- 1.4 mM (P < 0.005), and mean glycated hemoglobin (HbA1) from 11.6 +/- 2.3% to 8.3 +/- 1.1% (P < 0.001). These changes were accompanied by a significant decrease in glycation of skin collagen, from 13.2 +/- 4.3 to 10.6 +/- 2.3 mmol FL/mol lysine (P < 0.002). However, levels of browning and oxidation products (pentosidine, CML, and CMhL) and fluorescence were unchanged. These results show that the glycation of long-lived proteins can be decreased by improved glycemic control, but suggest that once cumulative damage to collagen by browning and oxidation reactions has occurred, it may not be readily reversed. Thus, in diabetic patients, institution and maintenance of good glycemic control at any time could potentially limit the extent of subsequent long-term damage to proteins by glycation and oxidation reactions.