Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects
Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects
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DOI：
10.2337/diabetes.53.3.624
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发表时间：
2004-03-01
期刊：
影响因子：
7.7
通讯作者：
Markmann, JF
中科院分区：
文献类型：
--
作者：
Deng, SP;Vatamaniuk, M;Markmann, JF
2型糖尿病患者既存在胰岛素作用紊乱，其胰岛细胞也有异常。后者究竟是原发性缺陷还是前者的结果尚不清楚。为了直接检测2型糖尿病患者胰岛的β细胞数量和功能，我们从2型糖尿病尸体捐赠者（n = 14）的胰腺中分离出胰岛，并将其与年龄、体重指数和冷缺血时间相匹配的正常捐赠者（n = 14）的胰岛进行比较。从2型糖尿病胰腺中回收的胰岛总量明显少于非糖尿病对照组（256,260个胰岛当量[2,588 IEq/克胰腺]对比597,569个胰岛当量[6,037 IEq/克胰腺]）。还注意到2型糖尿病胰岛平均较小，从组织学上看，糖尿病患者的胰岛中产生胰高血糖素的α细胞比例较高。对糖尿病患者胰岛功能的体外研究显示，在灌流实验中，葡萄糖刺激的胰岛素释放反应异常。此外，与正常胰岛相比，相同数量的2型糖尿病胰岛移植到免疫缺陷型糖尿病小鼠体内时无法逆转高血糖。这些结果为2型糖尿病患者胰岛的异常提供了直接证据，这些异常可能导致该疾病的发病机制。
Type 2 diabetic subjects manifest both disordered insulin action and abnormalities in their pancreatic islet cells. Whether the latter represents a primary defect or is a consequence of the former is unknown. To examine the beta-cell mass and function of islets from type 2 diabetic patients directly, we isolated islets from pancreata of type 2 diabetic cadaveric donors (n = 14) and compared them with islets from normal donors (n = 14) matched for age, BMI, and cold ischemia time. The total recovered islet mass from type 2 diabetic pancreata was significantly less than that from nondiabetic control subjects (256,260 islet equivalents [2,588 IEq/g pancreas] versus 597,569 islet equivalents [6,037 IEq/g pancreas]). Type 2 diabetic islets were also noted to be smaller on average, and histologically, islets from diabetic patients contained a higher proportion of glucagon-producing alpha-cells. In vitro study of islet function from diabetic patients revealed an abnormal glucose-stimulated insulin release response in perifusion assays. In addition, in comparison with normal islets, an equivalent number of type 2 diabetic islets failed to reverse hyperglycemia when transplanted to immunodeficient diabetic mice. These results provide direct evidence for abnormalities in the islets of type 2 diabetic patients that may contribute to the pathogenesis of the disease.