One potential model of type 2 diabetes etiology is that those with the disease were born with less β-cell mass making them susceptible to stressors such as obesity. Thus, it would be of therapeutic potential to find mechanisms that increase functional β-cell mass. One candidate that has been studied in our lab is Connective tissue growth factor (Ctgf). Ctgf is a secreted protein known to be involved in cell adhesion, migration and, in some cell types, proliferation. Previous studies in our lab have shown that Ctgf is crucial for β-cell development, with loss of Ctgf resulting in fewer β-cells and decreased β-cell proliferation, thus decreased β-cell mass at birth. Ctgf is also important in situations of metabolic stress, such as pregnancy or β-cell loss. Haploinsufficiency during pregnancy results in decreased maternal β-cell proliferation while in contrast, over-expression of Ctgf results in increased β-cell proliferation and regeneration in a model of partial β-cell ablation. Treatment of human and mouse islets ex vivo with recombinant human Ctgf (rhCTGF) has resulted in increased β-cell proliferation. To determine whether smaller fragments of the 40 kD Ctgf protein can promote proliferation, mouse and human islets were treated with either an N-or C-terminal fragment independently.

Results show that N-terminal Ctgf is responsible for promoting β-cell proliferation in both mouse and human islets. Further studies will elucidate the mechanisms by which Ctgf promotes β-cell proliferation as well as through what receptor it acts on β-cells.


S.E. Townsend: None. R. Pasek: None. M.A. Cottam: None. M.A. Gannon: None.

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