Malaisse W J
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Horm Metab Res. 1991 Jul;23(7):307-11. doi: 10.1055/s-2007-1003684.
In non-insulin-dependent diabetic subjects and in various animal models of spontaneous or experimental chronic hyperglycaemia, the secretory response of the pancreatic B-cell to a rapid rise in extracellular D-glucose concentration is characterized by a paradoxical, early and transient fall in insulin output and/or an altered anomeric specificity. These two features of B-cell glucotoxicity may be accounted for by the accumulation of glycogen in the B-cell and the interference of changes in glycogenolysis with the hexose-induced increase in glycolytic flux. The inhibitory action of D-glucose upon glycogenolysis displaying alpha-stereospecificity, the metabolic and secretory response to alpha-D-glucose is expected to be more severely affected than that evoked by the beta-anomer. Such a preferential alteration of the response to alpha-D-glucose was indeed documented in diabetic subjects, BB rats, duct-ligated rabbits, and adult rats either injected with streptozotocin during the neonatal period or rendered hyperglycaemic by the repeated administration of diazoxide. In these experimental models, the attenuation, suppression or even reversal of the anomeric preference in insulin release appeared related to the severity and duration of the hyperglycaemic state. A clear distinction ought to be made between these features of B-cell glucotoxicity and other etiopathogenic factors of B-cell dysfunction, such as the long term deleterious effect of streptozotocin upon the activity of key mitochondrial dehydrogenases.
在非胰岛素依赖型糖尿病患者以及各种自发性或实验性慢性高血糖动物模型中，胰腺β细胞对细胞外D - 葡萄糖浓度快速升高的分泌反应的特征是胰岛素分泌出现反常、早期且短暂的下降和/或异头特异性改变。β细胞糖毒性的这两个特征可能是由于糖原在β细胞中的积累以及糖原分解变化对己糖诱导的糖酵解通量增加的干扰所致。由于D - 葡萄糖对糖原分解的抑制作用表现出α - 立体特异性，预计对α - D - 葡萄糖的代谢和分泌反应比β - 异头物引起的反应受到更严重的影响。在糖尿病患者、BB大鼠、胆管结扎的兔子以及新生期注射链脲佐菌素或通过反复给予二氮嗪而致高血糖的成年大鼠中，确实记录到了对α - D - 葡萄糖反应的这种优先改变。在这些实验模型中，胰岛素释放中异头偏好的减弱、抑制甚至逆转似乎与高血糖状态的严重程度和持续时间有关。应该明确区分β细胞糖毒性的这些特征与β细胞功能障碍的其他病因学因素，例如链脲佐菌素对关键线粒体脱氢酶活性的长期有害影响。
