Zhang Xiaoboo, Gaspard John P, Mizukami Yusuke, Li Jingnan, Graeme-Cook Fiona, Chung Daniel C
Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital Harvard Medical, 70 Blossom St., Boston, MA 02114, USA.
Diabetes. 2005 Mar;54(3):712-9. doi: 10.2337/diabetes.54.3.712.
Cyclin D1 can stimulate proliferation by driving cells from the G1 into the S-phase of the mammalian cell cycle. Previous animal studies have implicated the G1-S transition as a key regulatory checkpoint governing the proliferation of pancreatic islet cells. We expressed cyclin D1 in the beta-cells of mice and islet hyperplasia developed in a time-dependent manner. The hyperplastic beta-cells exhibited higher rates of proliferation. However, blood glucose levels in fasting as well as nonfasting conditions remained normal. Furthermore, glucose tolerance tests demonstrated nearly normal responses, and diabetes did not develop in any of the animals. No islet cell tumors were observed, even among animals >2 years of age. Under our experimental conditions, the proliferative stimulus provided by cyclin D1 is not tumorigenic, does not result in diabetes, and does not result in hypoglycemia. Cyclin D1 may thus be considered a potential candidate to augment the beta-cell population ex vivo as a prelude to islet transplantation for diabetes.
细胞周期蛋白D1可通过促使细胞从G1期进入哺乳动物细胞周期的S期来刺激细胞增殖。先前的动物研究表明，G1-S转换是控制胰岛细胞增殖的关键调控检查点。我们在小鼠的β细胞中表达细胞周期蛋白D1，胰岛增生呈时间依赖性发展。增生的β细胞表现出更高的增殖率。然而，禁食和非禁食条件下的血糖水平均保持正常。此外，葡萄糖耐量试验显示反应几乎正常，且所有动物均未发生糖尿病。即使在2岁以上的动物中也未观察到胰岛细胞瘤。在我们的实验条件下，细胞周期蛋白D1提供的增殖刺激不会致癌，不会导致糖尿病，也不会导致低血糖。因此，细胞周期蛋白D1可被视为一种潜在的候选物质，用于在体外增加β细胞数量，作为糖尿病胰岛移植的前奏。
