REDUCED BETA-CELL GLUCOSE TRANSPORTER IN NEW ONSET DIABETIC BB RATS

REDUCED BETA-CELL GLUCOSE TRANSPORTER IN NEW ONSET DIABETIC BB RATS
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DOI:
10.1172/jci114883
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发表时间:
1990-11-01
影响因子:
15.9
通讯作者:
THORENS, B
THORENS, B
中科院分区:
医学1区
文献类型:
--
作者:
ORCI, L;UNGER, RH;THORENS, B

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我们实验室以前的研究表明,在明显糖尿病的第一天从BB大鼠分离的胰岛中葡萄糖转运存在缺陷。通过免疫染色定量β-葡萄糖转运,在自身免疫性糖尿病之前和发病时,我们使用了针对其COOH末端八肽的抗体。在明显糖尿病的第一天,定义为每日血糖首次达到200 mg/dl的那天,GLUT-2阳性与胰岛素阳性β-葡萄糖的体积密度比为200 mg/dl。细胞数仅为0.48 ± 0.48。0.06,而0.91 ±。0.02在年龄匹配的非糖尿病糖尿病耐药对照组中(P < 0.001)。在年龄匹配的非糖尿病糖尿病易感大鼠中,其中大多数将成为糖尿病,该比率为0.85 ± 0.05。0.02,也低于对照组(P < 0.05)。蛋白A-金标记的β-葡萄糖基转移酶中GLUT-2细胞1糖尿病大鼠显示2.17 ±。0.16微绒毛质膜每微米长度的金颗粒与3.9 ±. 0.14对照组(P < 0.001)和2.87 ±. 0.24而非糖尿病易感大鼠则明显高于对照组(P < 0.02)。GLUT-2的减少与葡萄糖刺激的胰岛素分泌的丧失在时间上相关,并且可能有助于葡萄糖刺激的胰岛素分泌的丧失,所述葡萄糖刺激的胰岛素分泌的丧失先于显著的β-胰岛素分泌。自身免疫性糖尿病的细胞耗竭
Previous studies from our laboratories have suggested a defect in glucose transport in islets isolated from BB rats on the first day of overt diabetes. To quantitate by immunostaining the glucose transport of .beta.-cells (GLUT-2) before and at the onset of autoimmune diabetes we employed an antibody to its COOH-terminal octapeptide. On the first day of overt diabetes, defined as the day the daily blood glucose first reached 200 mg/dl, the volume density ratio of GLUT-2-positive to insulin-positive .beta.-cells was only 0.48 .+-. 0.06, compared to 0.91 .+-. 0.02 in age-matched nondiabetic diabetes-resistant controls (P < 0.001). In age-matched nondiabetic diabetes-prone rats, most of which would have become diabetic, the ratio was 0.85 .+-. 0.02, also less than the controls (P < 0.05). Protein A-gold labeling of GLUT-2 in .beta.-cell 1 diabetic rats revealed 2.17 .+-. 0.16 gold particles per micrometer length of microvillar plasma membranes compared to 3.9 .+-. 0.14 in controls (P < 0.001) and 2.87 .+-. 0.24 in the nondiabetic diabetes-prone rats (P < 0.02). Reduction in GLUT-2 correlates temporally with and may contribute to the loss of glucose-stimulated insulin secretion that precedes profound .beta.-cell depletion of autoimmune diabetes.