Glucokinase activation as antidiabetic therapy: effect of nutraceuticals and phytochemicals on glucokinase gene expression and enzymatic activity

Abstract

Diabetes represents an important public health problem. Recently, new molecular targets have been identified and exploited to treat this disease. Due to its pivotal role in glucose homeostasis, glucokinase (GCK) is a promising target for the development of novel antidiabetic drugs; however, pharmacological agents that modulate GCK activity have been linked to undesirable side-effects, limiting its use. Interestingly, plants might be a valuable source of new therapeutic compounds with GCK-activating properties and presumably no adverse effects. In this review, we describe biochemical characteristics related to the physiological and pathological importance of GCK, as well as the mechanisms involved in its regulation at different molecular levels. Posteriorly, we present a compendium of findings supporting the potential use of nutraceuticals and phytochemicals in the management of diabetes through modulation of GCK expression and activity. Finally, we propose critical aspects to keep in mind when designing experiments to evaluate GCK modulation properly.

Keywords:

• Diabetes
• glucokinase
• hypoglycaemic agents
• pharmacological mechanisms of action
• plant-derived compounds

Acknowledgements

The authors are indebted to Dr. Salvador García-López for his helpful comments and critical review of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The present study was supported by Consejo Nacional de Ciencia y Tecnología (CONACyT) grant (number 60283) awarded to CMGD. Partial financial support was also received from the Universidad de Guadalajara REC/198/2017 and REC/164/2017. TJG received a fellowship from CONACyT (fellowship 598227).