Dual effect of reduced type I diacylglycerol kinase activity on insulin secretion from MIN6 β-cells
The role of type I diacylglycerol kinases (DGKs) in the regulation of insulin secretion was investigated in MIN6 β-cells. In intracellular Ca2+ concentration ([Ca2+]i) measurement experiments, 1 μM R59949, a type I DGK inhibitor, and 10 μM DiC8, a diacylglycerol (DAG) analog, amplified 22.2 mM gluco...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-06-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319341659 |
| _version_ | 1811214878775443456 |
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| author | Toshiaki Sawatani Yukiko K. Kaneko Tomohisa Ishikawa |
| author_facet | Toshiaki Sawatani Yukiko K. Kaneko Tomohisa Ishikawa |
| author_sort | Toshiaki Sawatani |
| collection | DOAJ |
| description | The role of type I diacylglycerol kinases (DGKs) in the regulation of insulin secretion was investigated in MIN6 β-cells. In intracellular Ca2+ concentration ([Ca2+]i) measurement experiments, 1 μM R59949, a type I DGK inhibitor, and 10 μM DiC8, a diacylglycerol (DAG) analog, amplified 22.2 mM glucose-induced [Ca2+]i oscillations in a protein kinase C (PKC)-dependent manner, whereas 10 μM R59949 and 100 μM DiC8 decreased [Ca2+]i independent of PKC. High concentrations of R59949 and DiC8 attenuated voltage-dependent Ca2+ channel currents. According to these results, 22.2 mM glucose-stimulated insulin secretion (GSIS) was potentiated by 1 μM R59949 but suppressed by 10 μM of the same. The DGKα inhibitor R59022 showed a similar dual effect. Conversely, DiC8 at 10 and 100 μM potentiated GSIS, although 100 μM DiC8 decreased [Ca2+]i. These results suggest that DAG accumulated through declined type I DGK activity shows a dual effect on insulin secretion depending on the degree of accumulation; a mild DAG accumulation induces a PKC-dependent stimulatory effect on insulin secretion, whereas an excessive DAG accumulation suppresses it in a PKC-independent manner, possibly via attenuation of VDCC activity. Keywords: Diacylglycerol, Diacylglycerol kinase, Insulin secretion, Intracellular Ca2+ concentration, Voltage-dependent Ca2+ channel |
| first_indexed | 2024-04-12T06:11:47Z |
| format | Article |
| id | doaj.art-84a0827a13314c359af2bf0f6ff72b90 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-12T06:11:47Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-84a0827a13314c359af2bf0f6ff72b902022-12-22T03:44:40ZengElsevierJournal of Pharmacological Sciences1347-86132019-06-011402178186Dual effect of reduced type I diacylglycerol kinase activity on insulin secretion from MIN6 β-cellsToshiaki Sawatani0Yukiko K. Kaneko1Tomohisa Ishikawa2Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, JapanCorresponding author.; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, JapanThe role of type I diacylglycerol kinases (DGKs) in the regulation of insulin secretion was investigated in MIN6 β-cells. In intracellular Ca2+ concentration ([Ca2+]i) measurement experiments, 1 μM R59949, a type I DGK inhibitor, and 10 μM DiC8, a diacylglycerol (DAG) analog, amplified 22.2 mM glucose-induced [Ca2+]i oscillations in a protein kinase C (PKC)-dependent manner, whereas 10 μM R59949 and 100 μM DiC8 decreased [Ca2+]i independent of PKC. High concentrations of R59949 and DiC8 attenuated voltage-dependent Ca2+ channel currents. According to these results, 22.2 mM glucose-stimulated insulin secretion (GSIS) was potentiated by 1 μM R59949 but suppressed by 10 μM of the same. The DGKα inhibitor R59022 showed a similar dual effect. Conversely, DiC8 at 10 and 100 μM potentiated GSIS, although 100 μM DiC8 decreased [Ca2+]i. These results suggest that DAG accumulated through declined type I DGK activity shows a dual effect on insulin secretion depending on the degree of accumulation; a mild DAG accumulation induces a PKC-dependent stimulatory effect on insulin secretion, whereas an excessive DAG accumulation suppresses it in a PKC-independent manner, possibly via attenuation of VDCC activity. Keywords: Diacylglycerol, Diacylglycerol kinase, Insulin secretion, Intracellular Ca2+ concentration, Voltage-dependent Ca2+ channelhttp://www.sciencedirect.com/science/article/pii/S1347861319341659 |
| spellingShingle | Toshiaki Sawatani Yukiko K. Kaneko Tomohisa Ishikawa Dual effect of reduced type I diacylglycerol kinase activity on insulin secretion from MIN6 β-cells Journal of Pharmacological Sciences |
| title | Dual effect of reduced type I diacylglycerol kinase activity on insulin secretion from MIN6 β-cells |
| title_full | Dual effect of reduced type I diacylglycerol kinase activity on insulin secretion from MIN6 β-cells |
| title_fullStr | Dual effect of reduced type I diacylglycerol kinase activity on insulin secretion from MIN6 β-cells |
| title_full_unstemmed | Dual effect of reduced type I diacylglycerol kinase activity on insulin secretion from MIN6 β-cells |
| title_short | Dual effect of reduced type I diacylglycerol kinase activity on insulin secretion from MIN6 β-cells |
| title_sort | dual effect of reduced type i diacylglycerol kinase activity on insulin secretion from min6 β cells |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319341659 |
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