title: Diacylglycerol kinase δ phosphorylates phosphatidylcholine-specific phospholipase C-dependent, palmitic acid-containing diacylglycerol species in response to high glucose levels.
abstract: Decreased expression of diacylglycerol (DG) kinase (DGK) δ in skeletal muscles is closely related to the pathogenesis of type 2 diabetes. To identify DG species that are phosphorylated by DGKδ in response to high glucose stimulation, we investigated high glucose-dependent changes in phosphatidic acid (PA) molecular species in mouse C2C12 myoblasts using a newly established liquid chromatography/MS method. We found that the suppression of DGKδ2 expression by DGKδ-specific siRNAs significantly inhibited glucose-dependent increases in 30:0-, 32:0-, and 34:0-PA and moderately attenuated 30:1-, 32:1-, and 34:1-PA. Moreover, overexpression of DGKδ2 also enhanced the production of these PA species. MS/MS analysis revealed that these PA species commonly contain palmitic acid (16:0). D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), significantly inhibited the glucose-stimulated production of the palmitic acid-containing PA species. Moreover, PC-PLC was co-immunoprecipitated with DGKδ2. These results strongly suggest that DGKδ preferably metabolizes palmitic acid-containing DG species supplied from the PC-PLC pathway, but not arachidonic acid (20:4)-containing DG species derived from the phosphatidylinositol turnover, in response to high glucose levels.
authors.affiliation: Department of Chemistry, Graduate School of Science and Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Center for Analytical Instrumentation, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522 and.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kado
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.affiliation: Department of Chemistry, Graduate School of Science and Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522. Electronic address: sakane@faculty.chiba-u.jp.
authors.forename: Fumio
authors.initials: F
authors.lastname: Sakane
mesh_terms: D000818:Animals; D002460:Cell Line; D019852:Diacylglycerol Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism*; D015870:Gene Expression; D005947:Glucose / Q000502:physiology*; D050356:Lipid Metabolism; D051379:Mice; D032446:Myoblasts / Q000201:enzymology; D019308:Palmitic Acid / Q000378:metabolism*; D010766:Phosphorylation; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D004075:Diglycerides; D019308:Palmitic Acid; D019852:Diacylglycerol Kinase; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C; D005947:Glucose
keywords: Diacylglycerol; Diacylglycerol Kinase; Glucose; Palmitic Acid; Phosphatidic Acid; Phosphatidylcholine-specific Phospholipase C; Phospholipase C; Type 2 Diabetes
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