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.

译文

:关于肠降血糖素疗法对胰腺β细胞的潜在再生影响与可能的不良胰腺增殖作用存在争议。通过降钙素治疗(n = 8)或其他治疗(n = 12)和非糖尿病对照组(n = 14)对年龄匹配的器官供体的2型糖尿病(DM)的胰腺进行检查,发现胰腺增加了约40%肠降血糖素治疗的DM肿块,外分泌细胞增殖增加(P <0.0001)和异型增生(胰腺上皮内瘤变增加,P <0.01)。用肠降血糖素治疗的DM中的胰腺显着表现为α细胞增生和表达胰高血糖素的微腺瘤(8个中的3个)和神经内分泌肿瘤。 DM患者的β细胞量减少了约60%,尽管用DM治疗的受试者仍能观察到,但接受降钙素治疗的患者的β细胞量却增加了6倍。与非DM对照组相比,DM内分泌胰岛素和胰高血糖素的内分泌细胞有所增加(P <0.05),而肠降血糖素治疗则明显增加了内分泌细胞(P <0.05)。总之,人类肠降血糖素疗法可导致胰腺内分泌和内分泌显着扩展,前者伴有增殖和发育异常,而后者则伴有α细胞增生,并有可能演变为神经内分泌肿瘤。

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