title: Overexpression of cyclin D1 in pancreatic beta-cells in vivo results in islet hyperplasia without hypoglycemia.
abstract: 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.
authors.affiliation: Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital Harvard Medical, 70 Blossom St., Boston, MA 02114, USA.
authors.forename: Xiaoboo
authors.initials: X
authors.lastname: Zhang
authors.forename: John P
authors.initials: JP
authors.lastname: Gaspard
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mizukami
authors.forename: Jingnan
authors.initials: J
authors.lastname: Li
authors.forename: Fiona
authors.initials: F
authors.lastname: Graeme-Cook
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Chung
mesh_terms: D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D005951:Glucose Tolerance Test; D006965:Hyperplasia / Q000503:physiopathology; D007003:Hypoglycemia / Q000503:physiopathology; D007515:Islets of Langerhans / Q000166:cytology* / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D001786:Blood Glucose; D019938:Cyclin D1