Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Diabetes. 2013 Jul;62(7):2595-604. doi: 10.2337/db12-1686. Epub 2013 Mar 22.
Controversy exists regarding the potential regenerative influences of incretin therapy on pancreatic β-cells versus possible adverse pancreatic proliferative effects. Examination of pancreata from age-matched organ donors with type 2 diabetes mellitus (DM) treated by incretin therapy (n = 8) or other therapy (n = 12) and nondiabetic control subjects (n = 14) reveals an ∼40% increased pancreatic mass in DM treated with incretin therapy, with both increased exocrine cell proliferation (P < 0.0001) and dysplasia (increased pancreatic intraepithelial neoplasia, P < 0.01). Pancreata in DM treated with incretin therapy were notable for α-cell hyperplasia and glucagon-expressing microadenomas (3 of 8) and a neuroendocrine tumor. β-Cell mass was reduced by ∼60% in those with DM, yet a sixfold increase was observed in incretin-treated subjects, although DM persisted. Endocrine cells costaining for insulin and glucagon were increased in DM compared with non-DM control subjects (P < 0.05) and markedly further increased by incretin therapy (P < 0.05). In conclusion, incretin therapy in humans resulted in a marked expansion of the exocrine and endocrine pancreatic compartments, the former being accompanied by increased proliferation and dysplasia and the latter by α-cell hyperplasia with the potential for evolution into neuroendocrine tumors.
关于肠促胰岛素治疗对胰腺β细胞的潜在再生影响与可能的不利胰腺增殖作用之间存在争议。检查年龄匹配的 2 型糖尿病（DM）患者的胰腺，这些患者接受肠促胰岛素治疗（n=8）或其他治疗（n=12）和非糖尿病对照受试者（n=14），结果显示接受肠促胰岛素治疗的 DM 患者胰腺质量增加了约 40%，外分泌细胞增殖（P<0.0001）和发育不良（胰腺上皮内瘤变增加，P<0.01）均增加。肠促胰岛素治疗的 DM 患者的胰腺以α细胞增生和胰高血糖素表达的微腺瘤（8 例中的 3 例）和神经内分泌肿瘤为特征。尽管 DM 持续存在，但β细胞质量减少了约 60%，但在接受肠促胰岛素治疗的患者中观察到增加了六倍。与非 DM 对照受试者相比，DM 患者的胰岛素和胰高血糖素共染色内分泌细胞增加（P<0.05），并且通过肠促胰岛素治疗进一步显著增加（P<0.05）。总之，肠促胰岛素治疗在人类中导致外分泌和内分泌胰腺区室明显扩张，前者伴有增殖和发育不良增加，后者伴有α细胞增生，并有演变为神经内分泌肿瘤的潜力。
