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 language | English |
|---|---|
| Pages (from-to) | 389-395 |
| Number of pages | 7 |
| Journal | Molecules and Cells |
| Volume | 32 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2011 Oct 1 |
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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 journal › Article
}
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 -