Present status of clinical deployment of glucokinase activators
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- Akinobu Nakamura
- Division of Immunology and Metabolism Hokkaido University Graduate School of Medicine Sapporo Japan
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- Yasuo Terauchi
- Department of Endocrinology and Metabolism Graduate School of Medicine Yokohama City University Yokohama Japan
書誌事項
- 公開日
- 2014-11-10
- 資源種別
- journal article
- 権利情報
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- http://creativecommons.org/licenses/by-nc/4.0/
- DOI
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- 10.1111/jdi.12294
- 公開者
- Wiley
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>Glucokinase is one of four members of the hexokinase family of enzymes. Its expression is limited to the major organs (such as the pancreas, liver, brain and the gastrointestinal tract) that are thought to have an integrated role in glucose sensing. In the liver, phosphorylation of glucose by glucokinase promotes glycogen synthesis, whereas in the β‐cells, it results in insulin release. Studies of glucokinase‐linked genetically‐modified mice and mutations in humans have illustrated the important roles played by glucokinase in whole‐body glucose homeostasis, and suggest that the use of pharmacological agents that augment glucokinase activity could represent a viable treatment strategy in patients with type 2 diabetes. Since 2003, many glucokinase activators (<jats:styled-content style="fixed-case">GKA</jats:styled-content>s) have been developed, and their ability to lower the blood glucose has been shown in several animal models of type 2 diabetes. Also, we and others have shown in mouse models that <jats:styled-content style="fixed-case">GKA</jats:styled-content>s also have the effect of stimulating the proliferation of β‐cells. However, the results of recent phase <jats:styled-content style="fixed-case">II</jats:styled-content> trials have shown that <jats:styled-content style="fixed-case">GKA</jats:styled-content>s lose their efficacy within several months of use, and that their use is associated with a high incidence of hypoglycemia; furthermore, patients treated with <jats:styled-content style="fixed-case">GKA</jats:styled-content>s frequently developed dyslipidemia. A better understanding of the role of glucokinase in metabolic effects is required to resolve several issues identified in clinical trials.</jats:p>
収録刊行物
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- Journal of Diabetes Investigation
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Journal of Diabetes Investigation 6 (2), 124-132, 2014-11-10
Wiley
