Triiodothyronine Induces Proliferation of Pancreatic β-cells through the MAPK/ERK Pathway

Abstract

Background:

3,5,3’-Triiodothyronine (T₃) has a stimulatory effect on cellular growth via thyroid hormone receptors (TRs) in several cell lines. TR expression in the pancreas suggests that pancreatic beta cell proliferation might be induced by T₃. The purpose of this study was to demonstrate that T₃ induces pancreatic beta cell proliferation through the mitogen activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway.

Methods:

INS-1 cells were plated as a monolayer at densities of 4×10⁴, cultured in RPMI 1 640 with 10% fetal bovine serum with 2-mercaptoethanol, respectively, in 6-well multiplates. After 48 h, they were exposed to 10⁻⁷ M T₃ or to vehicle alone. Viable cells were harvested after 24, 48, and 72 h of continuous exposure. Cell proliferation and TRα1 and TRβ1 expression were analyzed by flow-assisted cell sorting analysis, Ki-67 staining, and Western blotting. The p38 MAPK, ERK, and Akt pathways were analyzed by Western blotting. Beta cell function was evaluated by assaying insulin secretion.

Results:

T₃ enhanced INS-1 cell proliferation at a dose of 10⁻⁷ M in a time-dependent manner via the MAPK/ERK pathway and promoted insulin secretion.

Conclusions:

Our results demonstrate that MAPK/ERK pathway plays an important role in the T₃ induced pancreatic beta cell proliferation.

Key words

3,5,3’-triiodothyronine (T3) - thyroid hormone receptors - INS-1 cell - MAPK/ERK pathway - Akt pathway

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