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

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

. Mol. Cells 2011;32:389-95. https://doi.org/10.1007/s10059-011-0157-9">
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Mol. Cells 2011; 32(4): 389-395

Published online September 7, 2011

https://doi.org/10.1007/s10059-011-0157-9

© The Korean Society for Molecular and Cellular Biology

Insulin Contributes to Fine-Tuning of the Pancreatic Beta-Cell Response to Glucagon-Like Peptide-1

Mi Jin Moon, Hee Young Kim1, Sumi Park, Dong-Kyu Kim, Eun Bee Cho, Jong-Ik Hwang, and Jae Young Seong*

Graduate School of Medicine, Korea University, Seoul 136-705, Korea, 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul 136-705, Korea

Correspondence to : *Correspondence: jyseong@korea.ac.kr

Received: July 29, 2011; Revised: August 15, 2011; Accepted: August 18, 2011

Abstract

Glucagon-like peptide-1 (GLP-1) stimulates insulin secre-tion from pancreatic ?-cells in a glucose-dependent man-ner. However, factors other than glucose that regulate the β-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 beta-cells. Pretreatment of beta-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 beta-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 beta-cells were exposed to high glucose for 18 h. Treatment of beta-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 in-hibitor, further augmented exe-4-induced cAMP forma-tion and Erk phosphorylation. These results suggest that insulin contributes to fine-tuning of the beta-cell response to GLP-1.

Keywords beta-cells, cAMP, Erk, GLP-1, insulin, RTK

Article

Research Article

Mol. Cells 2011; 32(4): 389-395

Published online October 31, 2011 https://doi.org/10.1007/s10059-011-0157-9

Copyright © The Korean Society for Molecular and Cellular Biology.

Insulin Contributes to Fine-Tuning of the Pancreatic Beta-Cell Response to Glucagon-Like Peptide-1

Mi Jin Moon, Hee Young Kim1, Sumi Park, Dong-Kyu Kim, Eun Bee Cho, Jong-Ik Hwang, and Jae Young Seong*

Graduate School of Medicine, Korea University, Seoul 136-705, Korea, 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul 136-705, Korea

Correspondence to:*Correspondence: jyseong@korea.ac.kr

Received: July 29, 2011; Revised: August 15, 2011; Accepted: August 18, 2011

Abstract

Glucagon-like peptide-1 (GLP-1) stimulates insulin secre-tion from pancreatic ?-cells in a glucose-dependent man-ner. However, factors other than glucose that regulate the β-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 beta-cells. Pretreatment of beta-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 beta-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 beta-cells were exposed to high glucose for 18 h. Treatment of beta-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 in-hibitor, further augmented exe-4-induced cAMP forma-tion and Erk phosphorylation. These results suggest that insulin contributes to fine-tuning of the beta-cell response to GLP-1.

Keywords: beta-cells, cAMP, Erk, GLP-1, insulin, RTK

Mol. Cells
Mar 31, 2023 Vol.46 No.3, pp. 131~189
COVER PICTURE
The physiologically important cytoprotective signaling in normal cells (background area in turquoise) mediated by NRF2 (blue chain) is often hijacked by cancer cells (red ball) in the tumor microenvironment (yellow area). However, the differential roles of NRF2 throughout the multistage carcinogenesis remains largely unresolved (white-colored overlapping misty areas).

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