Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959

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Glucokinase as a therapeutic target based on findings from the analysis of mouse models
Akinobu Nakamura
著者情報
キーワード: Beta-cell, Glucokinase, Knockout mouse
ジャーナル フリー 早期公開

論文ID: EJ21-0742

この記事には本公開記事があります。
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I investigated mouse models to elucidate the pathophysiology and to establish a new treatment strategy for type 2 diabetes, with a particular focus on glucokinase. The decrease in pancreatic beta-cell function and mass are important factors in the pathophysiology of type 2 diabetes. My group have shown that glucokinase plays an important role in high-fat diet-induced and high-starch diet-induced beta-cell expansion. The findings indicated that the mechanism of short-term high-fat diet-induced beta-cell proliferation involved a glucokinase-independent pathway, suggesting that there are different pathways and mechanisms in the proliferation of pancreatic beta-cells during short-term versus long-term high-fat diets. Because enhancement of glucose signals via glucokinase is important for beta-cell proliferation, it was thought that beta-cell mass would be increased and insulin secretion would be maintained by glucokinase activators. However, sub-chronic administration of a glucokinase activator in db/db mice produced an unsustained hypoglycemic effect and promoted hepatic fat accumulation without changes in beta-cell function and mass. In contrast, my group have shown that inactivating glucokinase in beta-cells prevented beta-cell failure and led to an improvement in glucose tolerance in db/db mice. Regulation of glucokinase activity has an influence on the pathophysiology of type 2 diabetes and can be one of the therapeutic targets.

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