Heaton D A, Lazarus N R, Pyke D A, Leslie R D
Department of Medicine, Kings College Hospital, London, UK.
Diabetologia. 1989 Nov;32(11):814-7. doi: 10.1007/BF00264913.
The B-cells of patients with recently diagnosed Type 1 (insulin-dependent) diabetes may have no response to glucose when the response to glucagon is present but attenuated. This observation suggests that the recognition of glucose is more severely affected than that for non-glucose stimulants. To determine whether a similar selective decrease in glucose response was present before the onset of diabetes we studied two groups of non-diabetic identical twins of patients with recently diagnosed Type 1 diabetes: one group with complement-fixing islet cell antibodies who were at high risk of developing diabetes (four of the five have already developed diabetes) and a group without such antibodies at low risk of developing diabetes. In addition, a group of patients with chronic pancreatitis were studied to control for non-specific damage to the B-cell. Responses to i.v. glucose and i.v. glucagon were compared. Patients with chronic pancreatitis has similar responses to both glucose and glucagon and the responses did not differ from control subjects. The B-cells of the immune positive group showed evidence of pathology because the insulin and C-peptide responses to both stimuli were reduced when compared to either their control subjects or the immune negative twin group. However, the B-cell response to both glucose and glucagon in the immune positive twins was similar. Because the B-cell response to glucose was not less than that to glucagon, a selective destruction of the glucose recognition system cannot be a characteristic of all twins throughout the period before they develop Type 1 diabetes.
近期诊断为1型(胰岛素依赖型)糖尿病患者的B细胞,在对胰高血糖素的反应存在但减弱时,可能对葡萄糖无反应。这一观察结果表明,与非葡萄糖刺激物相比,葡萄糖的识别受到的影响更为严重。为了确定在糖尿病发病前是否也存在类似的葡萄糖反应选择性降低,我们研究了两组近期诊断为1型糖尿病患者的非糖尿病同卵双胞胎:一组有补体结合胰岛细胞抗体,患糖尿病风险高(五人中四人已患糖尿病),另一组无此类抗体,患糖尿病风险低。此外,还研究了一组慢性胰腺炎患者,以控制B细胞的非特异性损伤。比较了静脉注射葡萄糖和静脉注射胰高血糖素后的反应。慢性胰腺炎患者对葡萄糖和胰高血糖素的反应相似,且与对照组无差异。免疫阳性组的B细胞显示出病理迹象,因为与对照组或免疫阴性双胞胎组相比,对两种刺激的胰岛素和C肽反应均降低。然而,免疫阳性双胞胎中B细胞对葡萄糖和胰高血糖素的反应相似。由于B细胞对葡萄糖的反应不低于对胰高血糖素的反应,因此在所有双胞胎发展为1型糖尿病之前的整个时期,葡萄糖识别系统的选择性破坏不可能是其特征。