Leclercq-Meyer V, Marchand J, Malaisse W J
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Horm Metab Res. 1991 Jun;23(6):257-61. doi: 10.1055/s-2007-1003668.
Mild hyperglycemia was induced in normal rats by oral administration of both diazoxide and D-glucose. After 48 hours of such a treatment, the insulin and glucagon secretory responses of the perfused pancreas to alpha- and beta-D-glucose (3.3 mM) were examined in the presence of 10.0 mM L-leucine. The output of insulin, but not that of glucagon, and the perfusion pressure were higher in treated than control rats. The alpha-anomer of D-glucose was a more potent insulin secretagogue than beta-D-glucose in both control and treated rats. However, the alpha/beta ratio in insulin output was twice higher in control than treated rats. By analogy with other experimental models of diabetes, the attenuation in the anomeric difference of glucose-stimulated insulin output in the treated rats could reflect an altered secretory response to alpha- rather than beta-D-glucose. These findings suggest that hyperglycemia provokes, as a function of its severity and duration, first attenuation and then suppression, if not inversion, of the anomeric preference for alpha-D-glucose in insulin release. They are also compatible with the hypothesis that the anomeric malaise, associated with B-cell glucotoxicity, is caused by a progressive accumulation of glycogen in this cell.
通过口服二氮嗪和D-葡萄糖在正常大鼠中诱导轻度高血糖。经过48小时的这种处理后，在10.0 mM L-亮氨酸存在的情况下，检测灌注胰腺对α-和β-D-葡萄糖（3.3 mM）的胰岛素和胰高血糖素分泌反应。与对照大鼠相比，处理组大鼠的胰岛素分泌量增加，但胰高血糖素分泌量未增加，且灌注压更高。在对照大鼠和处理组大鼠中，D-葡萄糖的α-异头物都是比β-D-葡萄糖更有效的胰岛素促分泌剂。然而，对照大鼠胰岛素分泌量的α/β比值比处理组大鼠高出两倍。与其他糖尿病实验模型类似，处理组大鼠中葡萄糖刺激的胰岛素分泌的异头物差异减弱可能反映了对α-D-葡萄糖而非β-D-葡萄糖的分泌反应改变。这些发现表明，高血糖根据其严重程度和持续时间，首先引起胰岛素释放中对α-D-葡萄糖的异头物偏好的减弱，然后是抑制，甚至可能是反转。它们也与以下假设一致，即与B细胞糖毒性相关的异头物不适是由该细胞中糖原的逐渐积累引起的。
