Variations of urinary protein excretion and α1-antitrypsin molecular size by glycemic control in type 2 diabetic patients

Mayuka Goya, Mie Arai, K. Yamanaka, Y. Kanai, K. Shiba, Kenji Sato
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Abstract

We tried to determine the variations of levels and molecular heterogeneities of various proteins which occur in type 2 diabetes patients during short-term hospitalization for glycemic control. Type 2 diabetes patients were classified into 2 groups: only oral diabetes medicine therapy (group I) and only insulin and/or insulin plus oral diabetes medicine therapy (group II). All urinary proteins in group I tended to decrease on discharge day. Tamm-Horsfall protein (THP) levels of group II significantly increased on discharge day. There were significant correlations between each protein except with THP on day of admission and discharge of group I. In addition, there were no correlations between THP and other proteins except with α1-antitrypsin (α1-AT) in group II. Comparison of blood glucose level and HbA1c on admission day and first clinic day after discharge revealed that HbA1c level on discharge day was significantly lower in group II. We examined the molecular size of various proteins by SDS-PAGE and western blotting. In both groups, 9 α1-AT bands of different molecular sizes were detected besides a main band, but in group II, a 43 kDa α1-AT fragment, in urine collected closer to discharge day was found to be more densely stained than that in urine collected on admission day. These results revealed that glycemic control by insulin increased THP levels, remarkably reduced other protein levels, and caused urinary α1-AT to be of low molecular size.
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2型糖尿病患者尿蛋白排泄及α1-抗胰蛋白酶分子大小与血糖控制的关系
我们试图确定2型糖尿病患者在短期血糖控制住院期间各种蛋白的水平变化和分子异质性。将2型糖尿病患者分为仅口服糖尿病药物治疗组(I组)和仅胰岛素和/或胰岛素加口服糖尿病药物治疗组(II组)。I组患者在出院当天尿蛋白均有降低的趋势。ⅱ组在出院当天THP水平显著升高。除ⅰ组入院和出院当天THP与其他蛋白均有显著相关性外,ⅱ组除α1-抗胰蛋白酶(α1-AT)外,其余蛋白与THP均无相关性。入院当日与出院后第1门诊日血糖、糖化血红蛋白水平比较,ⅱ组患者出院当日糖化血红蛋白水平明显降低。我们用SDS-PAGE和western blotting检测了各种蛋白的分子大小。两组患者除1条主带外,均检测到9条不同分子大小的α1-AT条带,但ⅱ组患者在出院当天尿液中发现一条43 kDa的α1-AT片段比入院当天尿液染色更密集。结果表明,胰岛素控制血糖可提高THP水平,显著降低其他蛋白水平,导致尿α1-AT低分子化。
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