3,5,3'-Triiodo-L-thyronine enhances the differentiation of a human pancreatic duct cell line (hPANC-1) towards a beta-cell-Like phenotype.
The thyroid hormone, 3,5,3'-Triiodo-L-thyronine (T3), is essential for growth, differentiation, and regulation of metabolic functions in multicellular organisms, although the specific mechanisms of this control are still unknown. In this study, treatment of a human pancreatic duct cell line (hPANC-1) with T3 blocks cell growth by an increase of cells in G(0)/G(1) cell cycle phase and enhances morphological and functional changes as indicated by the marked increase in the synthesis of insulin and the parallel decrease of the ductal differentiation marker cytokeratin19. Expression analysis of some of the genes regulating pancreatic beta-cell differentiation revealed a time-dependent increase in insulin and glut2 mRNA levels in response to T3. As last step of the acquisition of a beta-cell-like phenotype, we present evidence that thyroid hormones are able to increase the release of insulin into the culture medium. In conclusion, our results suggest, for the first time, that thyroid hormones induce cell cycle perturbations and play an important role in the process of transdifferentiation of a human pancreatic duct line (hPANC-1) into pancreatic-beta-cell-like cells. These findings have important implications in cell-therapy based treatment of diabetes and may provide important insights in the designing of novel therapeutic agents to restore normal glycemia in subjects with diabetes.
Misiti
Silvia
S
Cattedra di Endocrinologia, II Facoltà di Medicina, Università di Roma "La Sapienza", Italy. silvia.misti@uniroma1.it
Anastasi
Emanuela
E
Sciacchitano
Salvatore
S
Verga Falzacappa
Cecilia
C
Panacchia
Laura
L
Bucci
Barbara
B
Khouri
Daniele
D
D'Acquarica
Ilaria
I
Brunetti
Ercole
E
Di Mario
Umberto
U
Toscano
Vincenzo
V
Perfetti
Riccardo
R
D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D051273:Glucose Transporter Type 2; D006801:Humans; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology* / Q000502:physiology; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000473:pathology*; D010641:Phenotype; D011988:Receptors, Thyroid Hormone / Q000235:genetics; D014284:Triiodothyronine / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine