Insulinoma induces a hyperinsulinemia-mediated decrease of GLUT2 and GLP1 receptor in normal pancreatic β-cells
Copyright © 2020 Elsevier Inc. All rights reserved..
There have been several clinical reports of transient postoperative hyperglycemia in patients with insulinoma, but the effect of insulinoma on normal β-cells has not been investigated. We examined the glucose transporter 2 (GLUT2) and glucagon-like peptide 1 receptor (GLP1R) expression in normal pancreatic β-cells of five patients with insulinoma and five patients with normal glucose tolerance (NGT) as controls. The positive rate of GLUT2-or GLP1R-positive islets in the nontumor area was calculated by the ratio with the analyzed islets. For functional in vitro analyses, q-PCR and Western blotting were performed after insulin loading on MIN6 cells. The expression rates of both GLUT2 and GLP1R were significantly lower in nontumor area islets of insulinoma patients than in patients with NGT (GLUT2: 31.6 ± 15.3% vs 95.9 ± 6.7%, p < 0.01, GLP1R: 66.8 ± 15.0% vs 96.7 ± 5.0%, p < 0.01). Exposure of MIN6 cells to high concentrations of insulin resulted in a significant decrease in GLUT2 protein for 12 h and GLP1R protein for 24 h (GLUT2; 1.00 ± 0.079 vs 0.81 ± 0.04. p = 0.02, GLP1R; 1.00 ± 0.10 vs 0.50 ± 0.24, p = 0.03) but not in those mRNAs. Our findings show that insulinoma is associated with the downregulation of GLUT2 and GLP1R expression in nontumor area islets. These phenomena may be caused by high levels of insulin.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:534 |
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| Enthalten in: |
Biochemical and biophysical research communications - 534(2021) vom: 01. Jan., Seite 702-706 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sho, H [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.04.2021 Date Revised 14.04.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2020.11.014 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a Sho, H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Insulinoma induces a hyperinsulinemia-mediated decrease of GLUT2 and GLP1 receptor in normal pancreatic β-cells |
| 264 | 1 | |c 2021 | |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a There have been several clinical reports of transient postoperative hyperglycemia in patients with insulinoma, but the effect of insulinoma on normal β-cells has not been investigated. We examined the glucose transporter 2 (GLUT2) and glucagon-like peptide 1 receptor (GLP1R) expression in normal pancreatic β-cells of five patients with insulinoma and five patients with normal glucose tolerance (NGT) as controls. The positive rate of GLUT2-or GLP1R-positive islets in the nontumor area was calculated by the ratio with the analyzed islets. For functional in vitro analyses, q-PCR and Western blotting were performed after insulin loading on MIN6 cells. The expression rates of both GLUT2 and GLP1R were significantly lower in nontumor area islets of insulinoma patients than in patients with NGT (GLUT2: 31.6 ± 15.3% vs 95.9 ± 6.7%, p < 0.01, GLP1R: 66.8 ± 15.0% vs 96.7 ± 5.0%, p < 0.01). Exposure of MIN6 cells to high concentrations of insulin resulted in a significant decrease in GLUT2 protein for 12 h and GLP1R protein for 24 h (GLUT2; 1.00 ± 0.079 vs 0.81 ± 0.04. p = 0.02, GLP1R; 1.00 ± 0.10 vs 0.50 ± 0.24, p = 0.03) but not in those mRNAs. Our findings show that insulinoma is associated with the downregulation of GLUT2 and GLP1R expression in nontumor area islets. These phenomena may be caused by high levels of insulin | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Glucagon-like peptide 1 receptor | |
| 650 | 4 | |a Glucose transporter 2 | |
| 650 | 4 | |a Insulinoma | |
| 650 | 4 | |a Pancreatic β-cell | |
| 650 | 4 | |a Postoperative hyperglycemia | |
| 650 | 7 | |a GLP1R protein, human |2 NLM | |
| 650 | 7 | |a Glp1r protein, mouse |2 NLM | |
| 650 | 7 | |a Glucagon-Like Peptide-1 Receptor |2 NLM | |
| 650 | 7 | |a Glucose Transporter Type 2 |2 NLM | |
| 650 | 7 | |a Insulin |2 NLM | |
| 650 | 7 | |a SLC2A2 protein, human |2 NLM | |
| 650 | 7 | |a Slc2a2 protein, mouse |2 NLM | |
| 700 | 1 | |a Fukui, K |e verfasserin |4 aut | |
| 700 | 1 | |a Yoneda, S |e verfasserin |4 aut | |
| 700 | 1 | |a Toyoda, S |e verfasserin |4 aut | |
| 700 | 1 | |a Ozawa, H |e verfasserin |4 aut | |
| 700 | 1 | |a Ishibashi, C |e verfasserin |4 aut | |
| 700 | 1 | |a Fujita, Y |e verfasserin |4 aut | |
| 700 | 1 | |a Eguchi, H |e verfasserin |4 aut | |
| 700 | 1 | |a Kozawa, J |e verfasserin |4 aut | |
| 700 | 1 | |a Shimomura, I |e verfasserin |4 aut | |
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