Bettin D, Klöting I, Kohnert K D
Institut für Diabetes Gerhardt Katsch der Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
Horm Metab Res. 1996 Jan;28(1):1-6. doi: 10.1055/s-2007-979119.
The CHIG/Han subline of the Chinese hamster develops noninsulin-dependent diabetes mellitus characterized by hyperinsulinemia and different degrees of glucose intolerance. To study whether these abnormalities could affect transmembrane cation transport activity, we determined membrane ATPase activity and ATP concentrations in red blood cells of diabetes-resistant CHIA and diabetes-susceptible CHIG sublines of the Chinese hamster. Mg(2+)-ATPase activity was increased in red blood cell membranes of diabetic hamsters compared with that of nondiabetic CHIG and the diabetes-resistant CHIA animals and correlated with plasma triglyceride and cholesterol levels. Ca(2+)-ATPase and Na+/K+ATPase activity were not significantly different between diabetic and nondiabetic hamsters, but for the Na+/K(+)-ATPase, Km was decreased and the Vmax value increased in membrane preparations from severely diabetic hamsters. Both ATP and ADP content were lower in erythrocytes from diabetic than nondiabetic hamsters. Independently of the levels of glycemia, AMP concentrations were higher in CHIG than in CHIA hamsters. While ATP/AMP ratios were found to be decreased in erythrocytes from diabetes-susceptible CHIG hamsters compared to the diabetes-resistant CHIA animals, they were significantly correlated with the levels of glycemia. Furthermore, the relationship between blood glucose levels and kidney weight in hamsters of the diabetes-susceptible CHIG subline was such, that severely hyperglycemic animals displayed the greatest increase in kidney wet weight. These results indicate that the progressive metabolic deterioration in the development of noninsulin-dependent diabetes is associated with significant changes in the activity and kinetic parameters of cellular ATPases which could probably indicate early membrane alterations which may eventually result in the late microangiopathic complications of diabetes.
中国仓鼠的CHIG/Han亚系会发展出以高胰岛素血症和不同程度的葡萄糖不耐受为特征的非胰岛素依赖型糖尿病。为了研究这些异常是否会影响跨膜阳离子转运活性，我们测定了中国仓鼠抗糖尿病的CHIA亚系和易患糖尿病的CHIG亚系红细胞中的膜ATP酶活性和ATP浓度。与非糖尿病的CHIG和抗糖尿病的CHIA动物相比，糖尿病仓鼠红细胞膜中的Mg(2+)-ATP酶活性增加，且与血浆甘油三酯和胆固醇水平相关。糖尿病和非糖尿病仓鼠之间的Ca(2+)-ATP酶和Na+/K+ATP酶活性没有显著差异，但对于Na+/K(+)-ATP酶，来自重度糖尿病仓鼠的膜制剂中Km降低而Vmax值增加。糖尿病仓鼠红细胞中的ATP和ADP含量均低于非糖尿病仓鼠。与血糖水平无关，CHIG仓鼠中的AMP浓度高于CHIA仓鼠。虽然发现易患糖尿病的CHIG仓鼠红细胞中的ATP/AMP比值低于抗糖尿病的CHIA动物，但它们与血糖水平显著相关。此外，在易患糖尿病的CHIG亚系仓鼠中，血糖水平与肾脏重量之间的关系是，严重高血糖的动物肾脏湿重增加最大。这些结果表明，非胰岛素依赖型糖尿病发展过程中的进行性代谢恶化与细胞ATP酶的活性和动力学参数的显著变化有关，这可能表明早期的膜改变，最终可能导致糖尿病的晚期微血管并发症。
