Morsiani E, Fogli L, Rozga J, Ricci D, Azzena G, Demetriou A A
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, Calif., USA.
Surgery. 1998 Apr;123(4):398-406.
Limitation of beta-cell growth after intraportal islet transplantation plays an important role in graft failure. To induce transplanted beta-cell proliferation, we studied the effect of compensatory liver growth in diabetic rats that had a subtherapeutic islet mass previously injected into the liver.
Syngeneic rats were used as islet donors or recipients; diabetes was induced by streptozocin. Three groups of streptozocin-treated rats were studied. In group 1, 250 islets were selectively transplanted into the posterior liver lobes and 10 days later anterior portal branch ligation (PBL) was performed (n = 18); in group 2, 250 islets were transplanted into the posterior lobes and 10 days later sham PBL was performed (n = 13); in group 3, rats underwent a sham transplantation and PBL (n = 6). Nonfasting blood glucose levels and body weight were monitored. Six rats in groups 1 and 2 were killed 48 hours after PBL, liver sections were stained for proliferating cell nuclear antigen, and islet cell labeling index was calculated. The remaining rats were killed 30 days later. Liver compensatory growth or atrophy was calculated and morphometric determination of beta-cell area was assessed on insulin-immunostained sections of the liver.
In group 1 rats killed 48 hours after PBL, islet cell labeling index was significantly higher than in group 2 (p < 0.0001). After PBL, we observed normalization of nonfasting blood glucose levels in 10 of 12 rats. At 30 days, posterior liver lobes showed compensatory growth (218.5% +/- 18.6%) accompanied by atrophy of the anterior lobes; morphometric study of liver-engrafted islets showed a significant increase of individual beta-cell area, compared with group 2 (p < 0.0001). In groups 2 and 3, normoglycemia was not achieved.
In streptozocin-diabetic rats, normoglycemia was restored after transplantation of a sub-therapeutic islet mass, followed by PBL-induced liver regeneration. Histologic and morphometric results indicating islet cell proliferation suggest that compensatory liver growth might have induced a hypertrophic/hyperplastic response in the intraportally transplanted beta-cells.
门静脉内胰岛移植后β细胞生长受限在移植物失败中起重要作用。为诱导移植的β细胞增殖，我们研究了在先前已向肝脏注射亚治疗剂量胰岛团块的糖尿病大鼠中代偿性肝脏生长的作用。
同基因大鼠用作胰岛供体或受体；用链脲佐菌素诱导糖尿病。研究了三组经链脲佐菌素治疗的大鼠。在第1组中，将250个胰岛选择性移植到肝脏后叶，10天后进行门静脉前支结扎（PBL）（n = 18）；在第2组中，将250个胰岛移植到后叶，10天后进行假PBL（n = 13）；在第3组中，大鼠接受假移植和PBL（n = 6）。监测非空腹血糖水平和体重。在PBL后48小时处死第1组和第2组中的6只大鼠，对肝脏切片进行增殖细胞核抗原染色，并计算胰岛细胞标记指数。其余大鼠在30天后处死。计算肝脏代偿性生长或萎缩情况，并在肝脏胰岛素免疫染色切片上评估β细胞面积的形态学测定。
在PBL后48小时处死的第1组大鼠中，胰岛细胞标记指数显著高于第2组（p < 0.0001）。PBL后，我们观察到12只大鼠中有10只非空腹血糖水平恢复正常。在30天时，肝脏后叶显示代偿性生长（218.5% +/- 18.6%），同时前叶萎缩；对移植到肝脏的胰岛进行形态学研究显示，与第2组相比，单个β细胞面积显著增加（p < 0.0001）。在第2组和第3组中，未实现血糖正常。
在链脲佐菌素诱导的糖尿病大鼠中，移植亚治疗剂量的胰岛团块后再进行PBL诱导的肝脏再生，血糖恢复正常。组织学和形态学结果表明胰岛细胞增殖，提示代偿性肝脏生长可能诱导了门静脉内移植的β细胞出现肥大/增生反应。
