3,5,3′-triiodothyronine (T3) is a survival factor for pancreatic β-cells undergoing apoptosis

3,5,3'-triiodothyronine (T-3) is essential for the growth and the regulation of metabolic functions, moreover, the growth-stimulatory effect of T-3 has largely been demonstrated and the pathways via which T-3 promotes cell growth have been recently investigated. Type 1 diabetes (T1D) is due to the destruction of beta-cells, which occurs even through apoptosis. Aim of our study was to analyze whether T-3 could have an antiapoptotic effect on cultured beta-cells undergoing apoptosis. We have demonstrated that T-3 promotes cell proliferation in islet beta-cell lines (rRINm5F and hCM) provoking an increment in cell number (up to 55%: rRINm5F and 45%: hCM), cell viability, and BrdU incorporation, and regulating the cell cycle-related molecules (cyc A, D1, E, and p27(kip1)). T-3 inhibited the apoptotic process induced by streptozocin, S-Nitroso-N-Acetylpenicylamine (SNAP), and H2O2 via regulation of the pro- and anti-apoptotic factors Bcl-2, Bcl-X-L, Bad, Bax, and Caspase 3. The T-3 protective effect was PI-3 K-, but not MAPK- or PKA-mediated, involving pAkt(Thr308). Thus, T-3 could be considered a survival factor protecting islet beta-cells from apoptosis.