| Autor: |
Kaneko YK; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka., Sawatani T; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka., Ishikawa T; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka. |
| Jazyk: |
japonština |
| Zdroj: |
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan [Yakugaku Zasshi] 2022; Vol. 142 (5), pp. 457-463. |
| DOI: |
10.1248/yakushi.21-00176-2 |
| Abstrakt: |
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 Ca 2+ 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 DiC 8 (a cell permeable DAG analog) enhanced glucose-induced [Ca 2+ ] i oscillation in a PKC-dependent manner, while 10 μM R59949 and 100 μM DiC 8 suppressed [Ca 2+ ] i oscillation and voltage-dependent Ca 2+ 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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