PSCs and GLP-1R

Occurrence in normal pancreas, acute/chronic pancreatitis and effect of their activation by a GLP-1R agonist

Taichi Nakamura, Tetsuhide Ito, Masahiko Uchida, Masayuki Hijioka, Hisato Igarashi, takamasa ono, Masaki Kato, Kazuhiko Nakamura, Koichi Suzuki, Robert T. Jensen, Ryoichi Takayanagi

研究成果: ジャーナルへの寄稿記事

12 引用 (Scopus)

抄録

There is increasing concern about the development of pancreatitis in patients with diabetes mellitus who received long-term glucagon-like peptide-1 (GLP-1) analog treatment. Its pathogenesis is unknown. The effects of GLP-1 agonists on pancreatic endocrine cells are well studied; however, there is little information on effects on other pancreatic tissues that might be involved in inflammatory processes. Pancreatic stellate cells (PSCs) can have an important role in pancreatitis, secreting various inflammatory cytokines/chemokines, as well as collagen. In this study, we investigated GLP-1R occurrence in normal pancreas, acute pancreatitis (AP)/chronic pancreatitis (CP), and the effects of GLP-1 analog on normal PSCs, their ability to stimulate inflammatory mediator secretion or proliferation. GLP-1 receptor (GLP-1R) expression/localization in normal pancreas and pancreatitis (AP/CP) tissues were evaluated with histological/immunohistochemical analysis. PSCs were isolated from male Wistar rats. GLP-1R expression and effects of GLP-1 analog on activated PSCs was examined with real-time PCR, MTS assays and western blotting. In normal pancreas, pancreatic β cells expressed GLP-1R, with only low expression in acinar cells, whereas in AP or CP, acinar cells, ductal cells and activated PSCs expressed GLP-1R. With activation of normal PSCs, GLP-1R is markedly increased, as is multiple other incretin-related receptors. The GLP-1 analog, liraglutide, did not induce inflammatory genes expression in activated PSCs, but induced proliferation. Liraglutide activated multiple signaling cascades in PSCs, and the extracellular signal-regulated kinase pathway mediated the PSCs proliferation. GLP-1Rs are expressed in normal pancreas and there is marked enhanced expression in AP/CP. GLP-1-agonist induced cell proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest chronic treatment with GLP-1R agonists could lead to proliferation/chronic activation of PSCs, which may lead to important effects in the pancreas.

元の言語英語
ページ(範囲)63-78
ページ数16
ジャーナルLaboratory Investigation
94
発行部数1
DOI
出版物ステータス出版済み - 1 1 2014

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Pancreatic Stellate Cells
Chronic Pancreatitis
Pancreas
Glucagon-Like Peptide 1
Pancreatitis
Acinar Cells
Cell Proliferation
Glucagon-Like Peptide-1 Receptor
Incretins
Endocrine Cells
Extracellular Signal-Regulated MAP Kinases
Chemokines

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

これを引用

PSCs and GLP-1R : Occurrence in normal pancreas, acute/chronic pancreatitis and effect of their activation by a GLP-1R agonist. / Nakamura, Taichi; Ito, Tetsuhide; Uchida, Masahiko; Hijioka, Masayuki; Igarashi, Hisato; ono, takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Jensen, Robert T.; Takayanagi, Ryoichi.

:: Laboratory Investigation, 巻 94, 番号 1, 01.01.2014, p. 63-78.

研究成果: ジャーナルへの寄稿記事

Nakamura, T, Ito, T, Uchida, M, Hijioka, M, Igarashi, H, ono, T, Kato, M, Nakamura, K, Suzuki, K, Jensen, RT & Takayanagi, R 2014, 'PSCs and GLP-1R: Occurrence in normal pancreas, acute/chronic pancreatitis and effect of their activation by a GLP-1R agonist', Laboratory Investigation, 巻. 94, 番号 1, pp. 63-78. https://doi.org/10.1038/labinvest.2013.133
Nakamura, Taichi ; Ito, Tetsuhide ; Uchida, Masahiko ; Hijioka, Masayuki ; Igarashi, Hisato ; ono, takamasa ; Kato, Masaki ; Nakamura, Kazuhiko ; Suzuki, Koichi ; Jensen, Robert T. ; Takayanagi, Ryoichi. / PSCs and GLP-1R : Occurrence in normal pancreas, acute/chronic pancreatitis and effect of their activation by a GLP-1R agonist. :: Laboratory Investigation. 2014 ; 巻 94, 番号 1. pp. 63-78.
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abstract = "There is increasing concern about the development of pancreatitis in patients with diabetes mellitus who received long-term glucagon-like peptide-1 (GLP-1) analog treatment. Its pathogenesis is unknown. The effects of GLP-1 agonists on pancreatic endocrine cells are well studied; however, there is little information on effects on other pancreatic tissues that might be involved in inflammatory processes. Pancreatic stellate cells (PSCs) can have an important role in pancreatitis, secreting various inflammatory cytokines/chemokines, as well as collagen. In this study, we investigated GLP-1R occurrence in normal pancreas, acute pancreatitis (AP)/chronic pancreatitis (CP), and the effects of GLP-1 analog on normal PSCs, their ability to stimulate inflammatory mediator secretion or proliferation. GLP-1 receptor (GLP-1R) expression/localization in normal pancreas and pancreatitis (AP/CP) tissues were evaluated with histological/immunohistochemical analysis. PSCs were isolated from male Wistar rats. GLP-1R expression and effects of GLP-1 analog on activated PSCs was examined with real-time PCR, MTS assays and western blotting. In normal pancreas, pancreatic β cells expressed GLP-1R, with only low expression in acinar cells, whereas in AP or CP, acinar cells, ductal cells and activated PSCs expressed GLP-1R. With activation of normal PSCs, GLP-1R is markedly increased, as is multiple other incretin-related receptors. The GLP-1 analog, liraglutide, did not induce inflammatory genes expression in activated PSCs, but induced proliferation. Liraglutide activated multiple signaling cascades in PSCs, and the extracellular signal-regulated kinase pathway mediated the PSCs proliferation. GLP-1Rs are expressed in normal pancreas and there is marked enhanced expression in AP/CP. GLP-1-agonist induced cell proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest chronic treatment with GLP-1R agonists could lead to proliferation/chronic activation of PSCs, which may lead to important effects in the pancreas.",
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AU - Igarashi, Hisato

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