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ID 109948
Title Alternative
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
Author
Kihira, Yoshitaka The University of Tokushima KAKEN Search Researchers
Burentogtokh, Ariunzaya The University of Tokushima
Itoh, Mari The University of Tokushima
Keywords
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
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Biological and Pharmaceutical Bulletin
ISSN
13475215
09186158
NCID
AA11696048
AA10885497
Publisher
The Pharmaceutical Society of Japan
Volume
38
Issue
4
Start Page
514
End Page
521
Published Date
2015-04-01
Remark
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第2966号
Diploma Number
甲医第1297号
Granted Date
2016-09-08
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
Pharmaceutical Sciences