Davalli A M, Ricordi C, Socci C, Braghi S, Bertuzzi F, Fattor B, Di Carlo V, Pontiroli A E, Pozza G
Istituto Scientifico San Raffaele, Cattedra di Clinica Medica, Università di Milano, Italy.
J Clin Endocrinol Metab. 1991 Jan;72(1):202-8. doi: 10.1210/jcem-72-1-202.
In the experimental animal chronic hyperglycemia alters the islet's sensitivity to glucose. In the present study the glucose sensitivity of human pancreatic islets, isolated and purified, obtained from seven human pancreases using an automated method was evaluated. After a 12-h stabilization period, islets were cultured for 48 h in normal (5.5 mmol/L) or high glucose (16.7 mmol/L) medium. Islets were then perifused to study their insulin response to glucose. Islets cultured in the high glucose medium lost glucose-induced insulin release and, when challenged with an acute fall of glucose concentration in the perifusate, showed a paradoxical insulin release. Insulin release in response to 10 mmol/L L-arginine was preserved in these islets, suggesting a selective reduction of the insulin response to glucose. An additional 48-h culture in 5.5 mmol/L glucose medium partially restored the sensitivity to glucose of the previously unresponsive islets. These findings indicate that short term exposure to high glucose concentrations induces a selective glucose insensitivity of human islets, which can be partially reversed by an additional culture in normal glucose medium.
在实验动物中，慢性高血糖会改变胰岛对葡萄糖的敏感性。在本研究中，使用自动化方法从七个人类胰腺中分离并纯化得到的人胰岛的葡萄糖敏感性进行了评估。经过12小时的稳定期后，胰岛在正常（5.5 mmol/L）或高糖（16.7 mmol/L）培养基中培养48小时。然后对胰岛进行灌流以研究其对葡萄糖的胰岛素反应。在高糖培养基中培养的胰岛失去了葡萄糖诱导的胰岛素释放，并且当灌流液中葡萄糖浓度急剧下降时，表现出反常的胰岛素释放。这些胰岛对1 mmol/L L-精氨酸的胰岛素释放得以保留，表明对葡萄糖的胰岛素反应有选择性降低。在5.5 mmol/L葡萄糖培养基中再培养48小时可部分恢复先前无反应的胰岛对葡萄糖的敏感性。这些发现表明，短期暴露于高糖浓度会诱导人胰岛产生选择性葡萄糖不敏感，通过在正常葡萄糖培养基中进一步培养可部分逆转这种情况。
