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 |
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
|
巻 | 38
|
号 | 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
|