Overexpression of Cyclin D1 in Pancreatic β-Cells In Vivo Results in Islet Hyperplasia Without Hypoglycemia

  1. Xiaoboo Zhang1,
  2. John P. Gaspard1,
  3. Yusuke Mizukami1,
  4. Jingnan Li1,
  5. Fiona Graeme-Cook2 and
  6. Daniel C. Chung1
  1. 1Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital Harvard Medical, Boston, Massachusetts
  2. 2Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
  1. Address correspondence and reprint requests to Daniel C. Chung, GRJ 825, Gastrointestinal Unit, Massachusetts General Hospital, 70 Blossom St., Boston, MA 02114. E-mail: chung.daniel{at}mgh.harvard.edu


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 β-cells of mice and islet hyperplasia developed in a time-dependent manner. The hyperplastic β-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 β-cell population ex vivo as a prelude to islet transplantation for diabetes.


    • Accepted November 29, 2004.
    • Received February 16, 2004.
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