IKdelay is related to a novel GLP-1 pathway that is KATP-independent insulin secretion.

IKdelay 与一种新的 GLP-1 途径相关，该途径不依赖于 KATP 的胰岛素分泌。

• 批准号: 20591071
• 负责人: KAKEI Masafumi
• 金额: $ 2.91万
• 依托单位: Jichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591071/
• 关键词: エネルギー; 糖質代謝異常; Kvチャネル; 膵β細胞; 膜電位; インスリン分泌; 脱リン酸化; カルシニューリン; 膜電位固定

IKdelay in pancreatic β-cells plays important roles in glucose-stimulated insulin secretion. IKdelay current is active during action potentials produced by glucose stimulation. Amplitudes of IKdelay are increased by increasing glucose concentrations from 2.8mM to 16.7mM. These increases were observed only at positive potentials were accompanied by the current decreases in the ranges of negative potentials. Conversely glucose reduction or metabolic inhibition by using FCCP, AMPPNP or 0mM ATP exposure at cytoplasm produced IKdelay increases at negative potentials associated with current decreases at positive potentials. We further observed the similar results in the HEK293 cells expressed with Kv2.1 channels during metabolic inhibition. Exposure to alkaline phosphatase at the cytoplasm showed current increases at negative potentials in Kv2.1 channel-expressed HEK293 cells. Thus, IKdelay changes observed in pancreatic β-cells during metabolic inhibition were resulted from the dephosphorylation of Kv2.1 channels because the channel protein has amino acid residues that can be highly phosphorylated at basal state. We concluded that Kv2.1 channel current is regulated by phosphorylation/dephosphorylation of the channel. These results may suggest that Kv2.1 channel regulation is involved in GLP-1 effect that is revealed with increases insulin secretion in the presence of the hormone.

胰腺 β 细胞中的 IK 延迟在葡萄糖刺激的胰岛素分泌中起着重要作用。 IKdelay 电流在葡萄糖刺激产生动作电位期间活跃。 IKdelay 的幅度通过将葡萄糖浓度从 2.8mM 增加到 16.7mM 来增加。仅在正电势范围内观察到这些增加，并伴随着负电势范围内的电流减少。相反，通过使用 FCCP、AMPPNP 或 0mM ATP 暴露在细胞质中进行葡萄糖减少或代谢抑制，产生的 IKdelay 在负电势下增加，而在正电势下电流减少。我们进一步在代谢抑制过程中用 Kv2.1 通道表达的 HEK293 细胞中观察到类似的结果。暴露于细胞质的碱性磷酸酶显示 Kv2.1 通道表达的 HEK293 细胞在负电位时电流增加。因此，在代谢抑制期间在胰腺β细胞中观察到的IK延迟变化是由Kv2.1通道去磷酸化引起的，因为该通道蛋白具有在基础状态下可以高度磷酸化的氨基酸残基。我们得出结论，Kv2.1 通道电流是通过通道的磷酸化/去磷酸化来调节的。这些结果可能表明 Kv2.1 通道调节参与了 GLP-1 效应，在激素存在的情况下，胰岛素分泌会增加。

项目成果

Regulation of voltage-gated K+ channels by glucose metabolism in pancreatic beta-cells.

胰腺 β 细胞中葡萄糖代谢对电压门控 K 通道的调节。

• 发表时间: 2009
• 期刊: Journal 583
• 作者: Yoshida;M.;Dezaki;K.;Yamato;S.;Aoki;A.;Sugawara;H.;Toyoshima;H.;Ishikawa;S. E.;Kawakami;M.;Nakata;M.;Yada;T.;Kakei;M.
• 通讯作者: M.

Deletion of CDKAL1 affects mitochondrial ATP generation and first-phase insulin exocytosis.

• DOI: 10.1371/journal.pone.0015553
• 发表时间: 2010-12-09
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Ohara-Imaizumi M;Yoshida M;Aoyagi K;Saito T;Okamura T;Takenaka H;Akimoto Y;Nakamichi Y;Takanashi-Yanobu R;Nishiwaki C;Kawakami H;Kato N;Hisanaga S;Kakei M;Nagamatsu S
• 通讯作者: Nagamatsu S

Low serum amylase in association with metabolic syndrome and diabetes: A community-based study.

• DOI: 10.1186/1475-2840-10-34
• 发表时间: 2011-04-17
• 期刊: Cardiovascular diabetology
• 影响因子: 9.3
• 作者: Nakajima K;Nemoto T;Muneyuki T;Kakei M;Fuchigami H;Munakata H
• 通讯作者: Munakata H

Voltage-dependent metabolic regulation of Kv2. 1 channels in pancreatic beta-cells.

Kv2 的电压依赖性代谢调节。

• 期刊: Biochem Biophyss Res Commun 28
• 作者: Yoshida M;Ishikawa S(6番目),(9名)
• 通讯作者: Ishikawa S(6番目),(9名)

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