3,5,3'-triiodothyronine (T3) is a survival factor for pancreatic beta-cells undergoing apoptosis.
3,5,3'-triiodothyronine (T3) is essential for the growth and the regulation of metabolic functions, moreover, the growth-stimulatory effect of T3 has largely been demonstrated and the pathways via which T3 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 T3 could have an antiapoptotic effect on cultured beta-cells undergoing apoptosis. We have demonstrated that T3 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)). T3 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-XL, Bad, Bax, and Caspase 3. The T3 protective effect was PI-3 K-, but not MAPK- or PKA-mediated, involving pAktThr308. Thus, T3 could be considered a survival factor protecting islet beta-cells from apoptosis.
Verga Falzacappa
Cecilia
C
Endocrinology, II Faculty of Medicine, University La Sapienza, Rome, Italy.
Panacchia
Laura
L
Bucci
Barbara
B
Stigliano
Antonio
A
Cavallo
Maria Gisella
MG
Brunetti
Ercole
E
Toscano
Vincenzo
V
Misiti
Silvia
S
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D014284:Triiodothyronine / Q000494:pharmacology / Q000502:physiology*
D016213:Cyclins; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019869:Phosphatidylinositol 3-Kinases