書誌事項
- タイトル別名
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- Involvement of Diacylglycerol Kinase on the Regulation of Insulin Secretion in Pancreatic β-Cells during Type 2 Diabetes
- スイvサイボウ シシツ タイシャ ブンシ ニ ヨル インスリン ブンピ セイギョ オヨビ 2ガタ トウニョウビョウ ビョウタイ ケイセイ エ ノ カンヨ
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抄録
<p>Depression of lipid metabolism in β-cells has been indicated to be one of the causes of impaired insulin secretion in type 2 diabetes. Diacylglycerol (DAG) is an important lipid mediator and is known to regulate insulin secretion in pancreatic β-cells. Intracellular DAG accumulation is involved in β-cell dysfunction in the pathogenesis of type 2 diabetes; thus, the regulation of intracellular DAG levels is likely important for maintaining the β-cell function. We focused on diacylglycerol kinases (DGKs), which strictly regulate intracellular DAG levels, and analyzed the function of type I DGKs (DGKα, γ), which are activated by intracellular Ca2+ and expressed in the cytoplasm, in β-cells. The suppression of the DGKα and γ expression decreased the insulin secretory response, and the decreased expression of DGKα and γ was observed in islets of diabetic model mice. In the pancreatic β-cell line MIN6, 1 μM R59949 (a type I DGK inhibitor) and 10 μM DiC8 (a cell permeable DAG analog) enhanced glucose-induced [Ca2+]i oscillation in a PKC-dependent manner, while 10 μM R59949 and 100 μM DiC8 suppressed [Ca2+]i oscillation and voltage-dependent Ca2+ channel activity in a PKC-independent manner. These results suggest that the intracellular accumulation of DAG by the loss of the DGKα and γ functions regulates insulin secretion in a dual manner depending on the degree of DAG accumulation. The regulation of the insulin secretory response through DAG metabolism by type I DGKs may change depending on the degree of progression of type 2 diabetes.</p>
収録刊行物
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- 薬学雑誌
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薬学雑誌 142 (5), 457-463, 2022-05-01
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390291932646300416
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- NII書誌ID
- AN00284903
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- ISSN
- 13475231
- 00316903
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- NDL書誌ID
- 032178782
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- NDL
- Crossref
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可