title: 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.
authors.affiliation: Department of Internal Medicine, College of Medicine, Inje University, Busan, Korea.
authors.forename: T K
authors.initials: TK
authors.lastname: Kim
authors.affiliation: Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Jung
authors.affiliation: Department of General Surgery, College of Medicine, Inje University, Busan, Korea.
authors.forename: T K
authors.initials: TK
authors.lastname: Ha
authors.affiliation: Department of Internal Medicine, College of Medicine, Inje University, Busan, Korea.
authors.forename: S M
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, Inje University, Busan, Korea.
authors.forename: N
authors.initials: N
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, College of Medicine, Inje University, Busan, Korea.
authors.forename: E J
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, College of Medicine, Inje University, Busan, Korea.
authors.forename: T N
authors.initials: TN
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, Inje University, Busan, Korea.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, College of Medicine, Inje University, Busan, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, College of Medicine, Inje University, Busan, Korea.
authors.forename: M K
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, Inje University, Busan, Korea.
authors.forename: B D
authors.initials: BD
authors.lastname: Rhee
authors.affiliation: Department of Internal Medicine, College of Medicine, Inje University, Busan, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D007211:Indoles / Q000737:chemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019394:Ki-67 Antigen / Q000737:chemistry; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D007211:Indoles; D007328:Insulin; D019394:Ki-67 Antigen; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; C007293:DAPI; D001973:Bromodeoxyuridine