First Phase of Glucose-Stimulated Insulin Secretion From MIN 6 Cells Does Not Always Require Extracellular Calcium Influx
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概要
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To demonstrate an involvement of ATP-sensitive potassium (KATP) channel-independent pathways in the first phase of glucose-stimulated insulin secretion (GSIS) from pancreatic β cells, the time course of GSIS from MIN6 cells was analyzed at 30-s sample intervals. GSIS was biphasic with the first phase being observed 120 to 390 s after glucose addition, peaking at 180 s, and with a shoulder at 240 to 330 s. Both 10 μM diazoxide and 3 μM verapamil completely inhibited tolbutamide- or glibenclamide-induced insulin secretion and suppressed the peak of the first phase of GSIS, but did not result in complete suppression. The shoulder following the peak was suppressed by 1 μM dantrolene. The peak, but not shoulder, disappeared under the extracellular Ca2+-free condition. A significant amount of insulin secretion remained even in the combined presence of verapamil and dantrolene. The Na+ channel blocker tetrodotoxin (30 nM) nearly completely inhibited the first phase release. These results suggest that the first phase of GSIS from MIN6 cells depends on both Ca2+-dependent and -independent mechanisms. The former mechanism includes the extracellular Ca2+ influx via L-type voltage-dependent calcium channel and intracellular Ca2+ release from endoplasmic reticulum via ryanodine receptors, and the latter mechanism involves the pathways associated with Na+ channels.
- 社団法人 日本薬理学会の論文
- 2006-08-20
著者
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Shigetoh Makoto
川崎医科大学 内科学教室内分泌糖尿病
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Shigeto Makoto
Division Of Diabetes And Endocrinology Department Of Medicine Kawasaki Medical School
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Shigeto Makoto
川崎医科大学 内科学(内分泌・糖尿病)
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KATSURA Masashi
Department of Pharmacology, Kawasaki Medical School
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MATSUDA Masafumi
Division of Diabetes and Endocrinology, Department of Medicine, Kawasaki Medical School
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OHKUMA Seitaro
Department of Pharmacology, Kawasaki Medical School
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KAKU Kohei
Division of Diabetes and Endocrinology, Department of Medicine, Kawasaki Medical School
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Kaku Kohei
Division Of Diabetes And Endocrinology Department Of Medicine Kawasaki Medical School
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Kaku Kohei
Division Of Diabetes And Endocrinology Department Of Internal Medicine Kawasaki Medical School
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Ohkuma Seitaro
Department Of Pharmacology Kawasaki Medical School
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Katsura Masashi
Department Of Pharmacology Kawasaki Medical School
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Katsura Masashi
Department Of Mathematics Faculty Of Science Kyoto Sangyo University
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Matsuda Masafumi
Division Of Diabetes And Endocrinology Department Of Medicine Kawasaki Medical School
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Matsuda Masafumi
Division Of Diabetes And Endocrinology Department Of Internal Medicine Kawasaki Medical School
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