TGF-β signalling prevents pancreatic beta cell death after proliferation.

Abstract

Maintenance of functional beta cell mass is critical for prevention of diabetes. The transforminggrowth factor-beta (TGF-β) receptor signalling pathway plays an essential role in pancreatic development. However, its involvement in control of post-natal beta cell growth has only been recently reported. Here, we studied the role of TGF-β receptor signalling in beta cell proliferation after 50% partial pancreatectomy (PPx), using beta cell-specific TGF-β receptor II (TBR2)-mutated mice. Consistent with previous reports, we found that inhibition of TGF-β receptor signalling in beta cells resulted in slightly higher beta cell mass 1week after PPx, due to greater beta cell proliferation. However, beta cell mass in these beta cell-specific TBR2-mutated mice significantly decreased by 12weeks after PPx, resulting from increase in beta cell apoptosis. Our data thus suggest that TGF-β receptor signalling may be required for prevention of beta cell death after proliferation, and highlight this pathway as an essential regulator during post-natal beta cell homoeostasis.