Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.
Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.
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发表时间：
2003
期刊：
影响因子：
7.7
通讯作者：
A. Butler;J. Janson;S. Bonner-Weir;R. Ritzel;R. Rizza;P. Butler
中科院分区：
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作者：
A. Butler;J. Janson;S. Bonner-Weir;R. Ritzel;R. Rizza;P. Butler
2型糖尿病的特征是胰岛素分泌受损。一些（但并非所有）研究表明，β细胞数量减少是导致这一情况的原因之一。我们检查了124例尸检的胰腺组织：91例肥胖病例（体重指数>27 kg/m²；其中41例患有2型糖尿病，15例空腹血糖受损[IFG]，35例非糖尿病患者）以及33例消瘦病例（体重指数<25 kg/m²；其中16例2型糖尿病患者，17例非糖尿病患者）。我们测量了相对β细胞体积、β细胞凋亡和增殖的频率，以及从外分泌导管形成新胰岛的情况（新生）。通过新生机制，肥胖的非糖尿病患者相对β细胞体积比消瘦的非糖尿病患者有所增加（P = 0.05）（P < 0.05）。与肥胖和消瘦的非糖尿病患者相比，肥胖的空腹血糖受损和2型糖尿病患者相对β细胞体积分别减少40%（P < 0.05）和63%（P < 0.01），消瘦的2型糖尿病患者相对β细胞体积减少41%（P < 0.05）。在所有病例中，β细胞增殖的频率都非常低，且各组之间无差异。新生情况虽然随着肥胖而增加，但在肥胖的2型糖尿病患者、空腹血糖受损患者或非糖尿病患者以及消瘦的2型糖尿病患者或非糖尿病患者中是相当的。然而，与各自的非糖尿病对照组相比，消瘦的2型糖尿病患者β细胞凋亡频率增加了10倍，肥胖的2型糖尿病患者增加了3倍（P < 0.05）。我们得出结论，2型糖尿病患者的β细胞数量减少，其潜在机制是β细胞凋亡增加。由于导致2型糖尿病患者β细胞数量减少的主要缺陷是凋亡增加，而新胰岛形成和β细胞增殖正常，因此旨在阻止凋亡的治疗方法可能是2型糖尿病治疗的一个重大新进展，因为这种方法实际上可能在一定程度上逆转疾病，而不仅仅是缓解血糖。
Type 2 diabetes is characterized by impaired insulin secretion. Some but not all studies suggest that a decrease in beta-cell mass contributes to this. We examined pancreatic tissue from 124 autopsies: 91 obese cases (BMI >27 kg/m(2); 41 with type 2 diabetes, 15 with impaired fasting glucose [IFG], and 35 nondiabetic subjects) and 33 lean cases (BMI <25 kg/m(2); 16 type 2 diabetic and 17 nondiabetic subjects). We measured relative beta-cell volume, frequency of beta-cell apoptosis and replication, and new islet formation from exocrine ducts (neogenesis). Relative beta-cell volume was increased in obese versus lean nondiabetic cases (P = 0.05) through the mechanism of increased neogenesis (P < 0.05). Obese humans with IFG and type 2 diabetes had a 40% (P < 0.05) and 63% (P < 0.01) deficit and lean cases of type 2 diabetes had a 41% deficit (P < 0.05) in relative beta-cell volume compared with nondiabetic obese and lean cases, respectively. The frequency of beta-cell replication was very low in all cases and no different among groups. Neogenesis, while increased with obesity, was comparable in obese type 2 diabetic, IFG, or nondiabetic subjects and in lean type 2 diabetic or nondiabetic subjects. However, the frequency of beta-cell apoptosis was increased 10-fold in lean and 3-fold in obese cases of type 2 diabetes compared with their respective nondiabetic control group (P < 0.05). We conclude that beta-cell mass is decreased in type 2 diabetes and that the mechanism underlying this is increased beta-cell apoptosis. Since the major defect leading to a decrease in beta-cell mass in type 2 diabetes is increased apoptosis, while new islet formation and beta-cell replication are normal, therapeutic approaches designed to arrest apoptosis could be a significant new development in the management of type 2 diabetes, because this approach might actually reverse the disease to a degree rather than just palliate glycemia.