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[Regulation of Lipid Metabolism by Diacylglycerol Kinases in Pancreatic β-cells].
Yakugaku Zasshi 2016; 136(3):461-5YZ

Abstract

The appropriate secretion of insulin from pancreatic β-cells is essential for regulating blood glucose levels. Glucose-stimulated insulin secretion (GSIS) involves the following steps: Glucose uptake by pancreatic β-cells is metabolized to produce ATP. Increased ATP levels result in the closure of ATP-sensitive K(+) (KATP) channels, resulting in membrane depolarization that activates voltage-dependent Ca(2+) channels to subsequently trigger insulin secretion. In addition to this primary mechanism through KATP channels, insulin secretion is regulated by cyclic AMP and diacylglycerol (DAG), which mediate the effects of receptor agonists such as GLP-1 and acetylcholine. Glucose by itself can also increase the levels of these second messengers. Recently, we have shown an obligatory role of diacylglycerol kinase (DGK), an enzyme catalyzing the conversion of DAG to phosphatidic acid, in GSIS. Of the 10 known DGK isoforms, we focused on type-I DGK isoforms (i.e., DGKα, DGKβ, and DGKγ), which are activated by Ca(2+). The protein expression of DGKα and DGKγ was detected in mouse pancreatic islets and the pancreatic β-cell line MIN6. Depletion of these DGKs by a specific inhibitor or siRNA decreased both [Ca(2+)]i and insulin secretion in MIN6 cells. Similar [Ca(2+)]i responses were induced by DiC8, a membrane-permeable DAG analog. These results suggest that DGKα and DGKγ play crucial roles in insulin secretion, and that their depletion impairs insulin secretion through DAG accumulation. In this article, we review the current understanding of the roles of DAG- and DGK-signaling in pancreatic β-cells, and discuss their pathophysiological roles in the progression of type-2 diabetes.

Authors+Show Affiliations

Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

jpn

PubMed ID

26935087

Citation

Kaneko, Yukiko K., and Tomohisa Ishikawa. "[Regulation of Lipid Metabolism By Diacylglycerol Kinases in Pancreatic Β-cells]." Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan, vol. 136, no. 3, 2016, pp. 461-5.
Kaneko YK, Ishikawa T. [Regulation of Lipid Metabolism by Diacylglycerol Kinases in Pancreatic β-cells]. Yakugaku Zasshi. 2016;136(3):461-5.
Kaneko, Y. K., & Ishikawa, T. (2016). [Regulation of Lipid Metabolism by Diacylglycerol Kinases in Pancreatic β-cells]. Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan, 136(3), pp. 461-5. doi:10.1248/yakushi.15-00246-1.
Kaneko YK, Ishikawa T. [Regulation of Lipid Metabolism By Diacylglycerol Kinases in Pancreatic Β-cells]. Yakugaku Zasshi. 2016;136(3):461-5. PubMed PMID: 26935087.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Regulation of Lipid Metabolism by Diacylglycerol Kinases in Pancreatic β-cells]. AU - Kaneko,Yukiko K, AU - Ishikawa,Tomohisa, PY - 2016/3/4/entrez PY - 2016/3/5/pubmed PY - 2017/1/10/medline SP - 461 EP - 5 JF - Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan JO - Yakugaku Zasshi VL - 136 IS - 3 N2 - The appropriate secretion of insulin from pancreatic β-cells is essential for regulating blood glucose levels. Glucose-stimulated insulin secretion (GSIS) involves the following steps: Glucose uptake by pancreatic β-cells is metabolized to produce ATP. Increased ATP levels result in the closure of ATP-sensitive K(+) (KATP) channels, resulting in membrane depolarization that activates voltage-dependent Ca(2+) channels to subsequently trigger insulin secretion. In addition to this primary mechanism through KATP channels, insulin secretion is regulated by cyclic AMP and diacylglycerol (DAG), which mediate the effects of receptor agonists such as GLP-1 and acetylcholine. Glucose by itself can also increase the levels of these second messengers. Recently, we have shown an obligatory role of diacylglycerol kinase (DGK), an enzyme catalyzing the conversion of DAG to phosphatidic acid, in GSIS. Of the 10 known DGK isoforms, we focused on type-I DGK isoforms (i.e., DGKα, DGKβ, and DGKγ), which are activated by Ca(2+). The protein expression of DGKα and DGKγ was detected in mouse pancreatic islets and the pancreatic β-cell line MIN6. Depletion of these DGKs by a specific inhibitor or siRNA decreased both [Ca(2+)]i and insulin secretion in MIN6 cells. Similar [Ca(2+)]i responses were induced by DiC8, a membrane-permeable DAG analog. These results suggest that DGKα and DGKγ play crucial roles in insulin secretion, and that their depletion impairs insulin secretion through DAG accumulation. In this article, we review the current understanding of the roles of DAG- and DGK-signaling in pancreatic β-cells, and discuss their pathophysiological roles in the progression of type-2 diabetes. SN - 1347-5231 UR - https://www.unboundmedicine.com/medline/citation/26935087/[Regulation_of_Lipid_Metabolism_by_Diacylglycerol_Kinases_in_Pancreatic_β_cells]_ L2 - https://dx.doi.org/10.1248/yakushi.15-00246-1 DB - PRIME DP - Unbound Medicine ER -