β-Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic β cells

Noriyuki Sonoda, Takeshi Imamura, Takeshi Yoshizaki, Jennie Bever, Juu Chin Lu, Jerrold M. Olefsky

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Glucagon-like peptide-1 (GLP-1) is a polypeptide hormone secreted from enteroendocrine L cells and potentiates glucose-dependent insulin secretion in pancreatic β cells. Recently the GLP-1 receptor (GLP-1 R) has been a focus for new anti-diabetic therapy with the introduction of GLP-1 analogues and DPP-IV inhibitors, and this has stimulated additional interest in the mechanisms of GLP-1 signaling. Here we identify a mechanism for GLP-1 action, showing that the scaffold protein β-arrestin-1 mediates the effects of GLP-1 to stimulate cAMP production and insulin secretion in β cells. Using a coimmunoprecipitation technique, we also found a physical association between the GLP-1 R and β-arrestin-1 in cultured INS-1 pancreatic β cells. β-Arrestin-1 knockdown broadly attenuated GLP-1 signaling, causing decreased ERK and CREB activation and IRS-2 expression as well as reduced cAMP levels and impaired insulin secretion. However, β-arrestin-1 knockdown did not affect GLP-1 R surface expression and ligand-induced GLP-1 R internalization/desensitization. Taken together, these studies indicate that β-arrestin-1 plays a role in GLP-1 signaling leading to insulin secretion, defining a previously undescribed mechanism for GLP-1 action.

Original languageEnglish (US)
Pages (from-to)6614-6619
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number18
DOIs
StatePublished - May 6 2008
Externally publishedYes

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Arrestin
Glucagon-Like Peptide 1
Cultured Cells
Insulin
Enteroendocrine Cells
Peptide Hormones

Keywords

  • CREB
  • IRS-2

ASJC Scopus subject areas

  • General

Cite this

β-Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic β cells. / Sonoda, Noriyuki; Imamura, Takeshi; Yoshizaki, Takeshi; Bever, Jennie; Lu, Juu Chin; Olefsky, Jerrold M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 18, 06.05.2008, p. 6614-6619.

Research output: Contribution to journalArticle

Sonoda, Noriyuki ; Imamura, Takeshi ; Yoshizaki, Takeshi ; Bever, Jennie ; Lu, Juu Chin ; Olefsky, Jerrold M. / β-Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic β cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 18. pp. 6614-6619.
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