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ID 109948
タイトル別表記
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
著者
木平, 孝高 The University of Tokushima KAKEN研究者をさがす
ブレントゴトホ, アリウンザヤ 徳島大学大学院医科学教育部(医学専攻)
Itoh, Mari The University of Tokushima
キーワード
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
資料タイプ
学位論文
抄録
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.
掲載誌名
Biological and Pharmaceutical Bulletin
ISSN
13475215
09186158
cat書誌ID
AA11696048
AA10885497
出版者
The Pharmaceutical Society of Japan
38
4
開始ページ
514
終了ページ
521
発行日
2015-04-01
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201611111001.pdf
論文本文 : LID201611111002.pdf
本論文は,著者Ariunzaya Burentogtokhの学位論文として提出され,学位審査・授与の対象となっている。
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2966号
学位記番号
甲医第1297号
学位授与年月日
2016-09-08
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
薬学系