First Phase of Glucose-Stimulated Insulin Secretion From MIN 6 Cells Does Not Always Require Extracellular Calcium Influx

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To demonstrate an involvement of ATP-sensitive potassium (K<sub>ATP</sub>) 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 Ca<sup>2+</sup>-free condition. A significant amount of insulin secretion remained even in the combined presence of verapamil and dantrolene. The Na<sup>+</sup> 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 Ca<sup>2+</sup>-dependent and -independent mechanisms. The former mechanism includes the extracellular Ca<sup>2+</sup> influx via L-type voltage-dependent calcium channel and intracellular Ca<sup>2+</sup> release from endoplasmic reticulum via ryanodine receptors, and the latter mechanism involves the pathways associated with Na<sup>+</sup> channels.<br>

収録刊行物

  • Journal of pharmacological sciences  

    Journal of pharmacological sciences 101(4), 293-302, 2006-08-20 

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10018236439
  • NII書誌ID(NCID)
    AA11806667
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13478613
  • NDL 記事登録ID
    8023015
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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