Insulin contributes to fine-tuning of the pancreatic beta-cell response to glucagon-like peptide-1

Mi Jin Moon, Hee Young Kim, Sumi Park, Dong Kyu Kim, Eun Bee Cho, Jong-Ik Hwang, Jae Young Seong

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic ß-cells in a glucose-dependent manner. However, factors other than glucose that regulate the ß-cell response to GLP-1 remain poorly understood. In this study, we examined the possible involvement of insulin and receptor tyrosine kinase signaling in regulation of the GLP-1 responsiveness of ß-cells. Pretreatment of ß-cells with HNMPA, an insulin receptor inhibitor, and AG1478, an epidermal growth factor receptor inhibitor, further increased the cAMP level and Erk phosphorylation in the presence of exendin-4 (exe-4), a GLP-1 agonist. When ß- cells were exposed to a high concentration of glucose (25 mM), which stimulates insulin secretion, exe-4-induced cAMP formation declined gradually as exposure time was increased. This decreased cAMP formation was not observed in the presence of HNMPA. HNMPA was able to further increase the exe-4-induced insulin secretion when ß-cells were exposed to high glucose for 18 h. Treatment of ß-cells with insulin significantly decreased exe-4- induced cAMP formation in a dose-dependent manner. Lowering the phospho-Akt level by HNMPA or LY294002, a PI3K inhibitor, further augmented exe-4-induced cAMP formation and Erk phosphorylation. These results suggest that insulin contributes to fine-tuning of the ß-cell response to GLP-1.

Original languageEnglish
Pages (from-to)389-395
Number of pages7
JournalMolecules and Cells
Volume32
Issue number4
DOIs
Publication statusPublished - 2011 Oct 1

Fingerprint

Glucagon-Like Peptide 1
Insulin-Secreting Cells
Insulin
Glucose
Phosphorylation
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Insulin Receptor
Phosphatidylinositol 3-Kinases
Epidermal Growth Factor Receptor
exenatide

Keywords

  • ß-cells
  • CAMP
  • Erk
  • GLP-1
  • Insulin
  • RTK

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Insulin contributes to fine-tuning of the pancreatic beta-cell response to glucagon-like peptide-1. / Moon, Mi Jin; Kim, Hee Young; Park, Sumi; Kim, Dong Kyu; Cho, Eun Bee; Hwang, Jong-Ik; Seong, Jae Young.

In: Molecules and Cells, Vol. 32, No. 4, 01.10.2011, p. 389-395.

Research output: Contribution to journalArticle

Moon, Mi Jin ; Kim, Hee Young ; Park, Sumi ; Kim, Dong Kyu ; Cho, Eun Bee ; Hwang, Jong-Ik ; Seong, Jae Young. / Insulin contributes to fine-tuning of the pancreatic beta-cell response to glucagon-like peptide-1. In: Molecules and Cells. 2011 ; Vol. 32, No. 4. pp. 389-395.
@article{c964c061cfc842fb95693670062cfda3,
title = "Insulin contributes to fine-tuning of the pancreatic beta-cell response to glucagon-like peptide-1",
abstract = "Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic {\ss}-cells in a glucose-dependent manner. However, factors other than glucose that regulate the {\ss}-cell response to GLP-1 remain poorly understood. In this study, we examined the possible involvement of insulin and receptor tyrosine kinase signaling in regulation of the GLP-1 responsiveness of {\ss}-cells. Pretreatment of {\ss}-cells with HNMPA, an insulin receptor inhibitor, and AG1478, an epidermal growth factor receptor inhibitor, further increased the cAMP level and Erk phosphorylation in the presence of exendin-4 (exe-4), a GLP-1 agonist. When {\ss}- cells were exposed to a high concentration of glucose (25 mM), which stimulates insulin secretion, exe-4-induced cAMP formation declined gradually as exposure time was increased. This decreased cAMP formation was not observed in the presence of HNMPA. HNMPA was able to further increase the exe-4-induced insulin secretion when {\ss}-cells were exposed to high glucose for 18 h. Treatment of {\ss}-cells with insulin significantly decreased exe-4- induced cAMP formation in a dose-dependent manner. Lowering the phospho-Akt level by HNMPA or LY294002, a PI3K inhibitor, further augmented exe-4-induced cAMP formation and Erk phosphorylation. These results suggest that insulin contributes to fine-tuning of the {\ss}-cell response to GLP-1.",
keywords = "{\ss}-cells, CAMP, Erk, GLP-1, Insulin, RTK",
author = "Moon, {Mi Jin} and Kim, {Hee Young} and Sumi Park and Kim, {Dong Kyu} and Cho, {Eun Bee} and Jong-Ik Hwang and Seong, {Jae Young}",
year = "2011",
month = "10",
day = "1",
doi = "10.1007/s10059-011-0157-9",
language = "English",
volume = "32",
pages = "389--395",
journal = "Molecules and Cells",
issn = "1016-8478",
publisher = "Korean Society for Molecular and Cellular Biology",
number = "4",

}

TY - JOUR

T1 - Insulin contributes to fine-tuning of the pancreatic beta-cell response to glucagon-like peptide-1

AU - Moon, Mi Jin

AU - Kim, Hee Young

AU - Park, Sumi

AU - Kim, Dong Kyu

AU - Cho, Eun Bee

AU - Hwang, Jong-Ik

AU - Seong, Jae Young

PY - 2011/10/1

Y1 - 2011/10/1

N2 - Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic ß-cells in a glucose-dependent manner. However, factors other than glucose that regulate the ß-cell response to GLP-1 remain poorly understood. In this study, we examined the possible involvement of insulin and receptor tyrosine kinase signaling in regulation of the GLP-1 responsiveness of ß-cells. Pretreatment of ß-cells with HNMPA, an insulin receptor inhibitor, and AG1478, an epidermal growth factor receptor inhibitor, further increased the cAMP level and Erk phosphorylation in the presence of exendin-4 (exe-4), a GLP-1 agonist. When ß- cells were exposed to a high concentration of glucose (25 mM), which stimulates insulin secretion, exe-4-induced cAMP formation declined gradually as exposure time was increased. This decreased cAMP formation was not observed in the presence of HNMPA. HNMPA was able to further increase the exe-4-induced insulin secretion when ß-cells were exposed to high glucose for 18 h. Treatment of ß-cells with insulin significantly decreased exe-4- induced cAMP formation in a dose-dependent manner. Lowering the phospho-Akt level by HNMPA or LY294002, a PI3K inhibitor, further augmented exe-4-induced cAMP formation and Erk phosphorylation. These results suggest that insulin contributes to fine-tuning of the ß-cell response to GLP-1.

AB - Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic ß-cells in a glucose-dependent manner. However, factors other than glucose that regulate the ß-cell response to GLP-1 remain poorly understood. In this study, we examined the possible involvement of insulin and receptor tyrosine kinase signaling in regulation of the GLP-1 responsiveness of ß-cells. Pretreatment of ß-cells with HNMPA, an insulin receptor inhibitor, and AG1478, an epidermal growth factor receptor inhibitor, further increased the cAMP level and Erk phosphorylation in the presence of exendin-4 (exe-4), a GLP-1 agonist. When ß- cells were exposed to a high concentration of glucose (25 mM), which stimulates insulin secretion, exe-4-induced cAMP formation declined gradually as exposure time was increased. This decreased cAMP formation was not observed in the presence of HNMPA. HNMPA was able to further increase the exe-4-induced insulin secretion when ß-cells were exposed to high glucose for 18 h. Treatment of ß-cells with insulin significantly decreased exe-4- induced cAMP formation in a dose-dependent manner. Lowering the phospho-Akt level by HNMPA or LY294002, a PI3K inhibitor, further augmented exe-4-induced cAMP formation and Erk phosphorylation. These results suggest that insulin contributes to fine-tuning of the ß-cell response to GLP-1.

KW - ß-cells

KW - CAMP

KW - Erk

KW - GLP-1

KW - Insulin

KW - RTK

UR - http://www.scopus.com/inward/record.url?scp=84855694178&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855694178&partnerID=8YFLogxK

U2 - 10.1007/s10059-011-0157-9

DO - 10.1007/s10059-011-0157-9

M3 - Article

C2 - 21904878

AN - SCOPUS:84855694178

VL - 32

SP - 389

EP - 395

JO - Molecules and Cells

JF - Molecules and Cells

SN - 1016-8478

IS - 4

ER -