ID 111099
著者
Yamamoto, Kiyotake Tokushima University
Tokashiki, Natsumi Tokushima University
Kobayashi, Makoto Tokushima University
キーワード
glucagon secretion
pancreatic α-cells
PKCδ
streptozotocin-induced diabetic mice
資料タイプ
学術雑誌論文
抄録
Accumulating evidence supports the “glucagonocentric hypothesis”, in which antecedent α-cell failure and inhibition of glucagon secretion are responsible for diabetes progression. Protein kinase C (PKC) is involved in glucagon secretion from α-cells, although which PKC isozyme is involved and the mechanism underlying this PKC-regulated glucagon secretion remains unknown. Here, the involvement of PKCδ in the onset and progression of diabetes was elucidated. Immunofluorescence studies revealed that PKCδ was expressed and activated in α-cells of STZ-induced diabetic model mice. Phorbol 12-myristate 13-acetate (PMA) stimulation significantly augmented glucagon secretion from isolated islets. Pre-treatment with quercetin and rottlerin, PKCδ signaling inhibitors, significantly suppressed the PMA-induced elevation of glucagon secretion. While Go6976, a Ca2+ - dependent PKC selective inhibitor did not suppress glucagon secretion. Quercetin suppressed PMA-induced phosphorylation of Tyr311 of PKCδ in isolated islets. However, quercetin itself had no effect on either glucagon secretion or glucagon mRNA expression. Our data suggest that PKCδ signaling inhibitors suppressed glucagon secretion. Elucidation of detailed signaling pathways causing PKCδ activation in the onset and progression of diabetes followed by the augmentation of glucagon secretion could lead to the identification of novel therapeutic target molecules and the development of novel therapeutic drugs for diabetes.
掲載誌名
The Journal of Medical Investigation
ISSN
13496867
13431420
cat書誌ID
AA11166929
AA12022913
出版者
Faculty of Medicine Tokushima University
64
1-2
開始ページ
122
終了ページ
128
並び順
122
発行日
2017-02
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
出版社版
部局
薬学系
先端酵素学研究所