Hypoxia Decreases Glucagon-Like Peptide-1 Secretion from the GLUTag Cell Line

• Material Type: 博士論文
• ISSN: 1347-5215
• Title: Hypoxia Decreases Glucagon-Like Peptide-1 Secretion from the GLUTag Cell Line
• Volume: 38 4
• Author/Editor: Kihira, Yoshitaka; Burentogtokh, Ariunzaya; Itoh, Mari; Izawa-Ishizawa, Yuki; Ishizawa, Keisuke; Ikeda, Yasumasa; Tsuchiya, Koichiro; Tamaki, Toshiaki
• Author Heading: Kihira, Yoshitaka; Burentogtokh, Ariunzaya; Itoh, Mari; Izawa-Ishizawa, Yuki; Ishizawa, Keisuke; Ikeda, Yasumasa; Tsuchiya, Koichiro; Tamaki, Toshiaki
• Publication, Distribution, etc.: The Pharmaceutical Society of Japan
• Publication Date: 2015-04-01
• Publication Date (W3CDTF): 2015-04-01
• Alternative Title: 低酸素はGLUTag細胞からのグルカゴン様ペプチド－１の分泌を抑制する
• Periodical title: Biological and Pharmaceutical Bulletin
• Degree grantor/type: 徳島大学
• Date Granted: 2016-09-08
• Date Granted (W3CDTF): 2016-09-08
• Dissertation Number: 甲第2966号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第2966号
• Text Language Code: eng
• Subject Heading: グルカゴン様ペプチド－１; 低酸素; 低酸素誘導因子; L細胞; 糖代謝; glucagon-like peptide-1; hypoxia; cAMP; hypoxia-inducible factor-1α; L cell
• Target Audience: 一般
• Note (General): Glucagon-like peptide-1 (GLP-1), an incretin hormone, is secreted from L cells located in the intestinal epithelium. It is known that intestinal oxygen tension is decreased postprandially. In addition, we found that the expression of hypoxia-inducible factor-1α (HIF-1α), which accumulates in cells under hypoxic conditions, was significantly increased in the colons of mice with food intake, indicating that the oxygen concentration is likely reduced in the colon after eating. Therefore, we hypothesized that GLP-1 secretion is affected by oxygen tension. We found that forskolin-stimulated GLP-1 secretion from GLUTag cells, a model of intestinal L cells, is suppressed in hypoxia (1% O2). Forskolin-stimulated elevations of preproglucagon (ppGCG) and proprotein convertase 1/3 (PC1/3) mRNA expression were decreased under hypoxic conditions. The finding that H89, a protein kinase A (PKA) inhibitor, inhibited the forskolin-stimulated increase of ppGCG and PC1/3 indicated that the cAMP-PKA pathway is involved in the hypoxia-induced suppression of the genes. Hypoxia decreased hexokinase 2 mRNA and protein expression and increased lactate dehydrogenase A mRNA and protein expression. Concomitantly, lactate production was increased and ATP production was decreased. Together, the results indicate that hypoxia decreases glucose utilization for ATP production, which probably causes a decrease in cAMP production and in subsequent GLP-1 production. Our findings suggest that the postprandial decrease in oxygen tension in the intestine attenuates GLP-1 secretion.
• DOI: info:doi/10.1248/bpb.b14-00612; https://doi.org/info:doi/10.1248/bpb.b14-00612
• Persistent ID (NDL): info:ndljp/pid/10224782; https://dl.ndl.go.jp/pid/10224782
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• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2016-12-01T22:39:34+09:00
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/109948
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