title: Glucagon-like peptide-1 stimulates type 3 iodothyronine deiodinase expression in a mouse insulinoma cell line.
abstract: OBJECTIVE
  The pathophysiological roles of thyroid hormones in glucose metabolism remain uncertain. Type 3 iodothyronine deiodinase (D3) converts thyroxine (T4) and 3,5,3'-triiodothyronine (T3) to 3,3',5'-triiodothyronine (rT3) and 3,3'-diiodothyronine (T2), respectively, inactivating thyroid hormones in a cell-specific fashion. In the present study, we identified D3 expression in MIN6 cells derived from a mouse insulinoma cell line and examined the mechanisms regulating D3 expression in these cells.
  
  
  METHODS
  We characterized D3 activity using HPLC analysis, and examined the effect of GLP-1 or exendin-4 on D3 expression and cAMP accumulation in MIN6 cells. We also measured insulin secretion from MIN6 cells exposed to GLP-1 and T3.
  
  
  RESULTS
  We identified enzyme activity that catalyzes the conversion of T3 to T2 in MIN6 cells, which showed characteristics compatible with those for D3. D3 mRNA was identified in these cells using RT-PCR analysis. Forskolin rapidly stimulated D3 mRNA and D3 activity. Glucagon-like peptide-1 (GLP-1) increased D3 expression in a dose-dependent manner, and this effect was inhibited by the protein kinase A (PKA) inhibitor H-89. Exendin-4, a GLP-1 receptor agonist, also stimulated D3 expression in MIN6 cells. These results suggest that a cAMP-PKA-mediated pathway participates in GLP-1-stimulated D3 expression in MIN6 cells. Furthermore, GLP-1 stimulated insulin secretion was suppressed by the addition of T3 in MIN6 cells.
  
  
  CONCLUSIONS
  Our findings indicate that GLP-1 regulates intracellular T3 concentration in pancreatic β cells via a cAMP-PKA-D3-mediated pathway that may also regulate β-cell function.
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Akiyama
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ogiwara
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Tsunekawa
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Araki
authors.affiliation: Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. Electronic address: mmurakam@gunma-u.ac.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D000077270:Exenatide; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D007340:Insulinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D014284:Triiodothyronine / Q000378:metabolism; D014285:Triiodothyronine, Reverse / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology
chemical_list: D010455:Peptides; D012333:RNA, Messenger; D014688:Venoms; D014284:Triiodothyronine; D005576:Colforsin; D014285:Triiodothyronine, Reverse; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D000242:Cyclic AMP; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Exendin-4; Glucagon-like peptide-1; Insulin; Mouse insulinoma cell line; Thyroid hormone; Type 3 iodothyronine deiodinase