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Editorial

Lessons from glucokinase activators: the problem of declining efficacy

Keep up to date with the latest research on this topic with citation updates for this article.

Read on this site (2)

Tereso J. Guzmán & Carmen M. Gurrola-Díaz. (2021) Glucokinase activation as antidiabetic therapy: effect of nutraceuticals and phytochemicals on glucokinase gene expression and enzymatic activity. Archives of Physiology and Biochemistry 127:2, pages 182-193.
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Markus Boehm, Matthew Crawford, Jamie E. Moscovitz & Philip A. Carpino. (2018) Diabetes area patent participation analysis – part II: years 2011-2016. Expert Opinion on Therapeutic Patents 28:2, pages 111-122.
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Articles from other publishers (29)

Wenjia Yang, Han Wu, Xiaoling Cai, Chu Lin, Ruoyang Jiao & Linong Ji. (2023) Evaluation of efficacy and safety of glucokinase activators—a systematic review and meta-analysis. Frontiers in Endocrinology 14.
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Siddharth Yadav, Samuel Bharti & Puniti Mathur. (2023) GlucoKinaseDB: A comprehensive, curated resource of glucokinase modulators for clinical and molecular research. Computational Biology and Chemistry 103, pages 107818.
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Ying Du, Leili Gao, Xinhua Xiao, Xin Hou & Linong Ji. (2022) A multicentre, randomized, double‐blind, parallel, active‐ and placebo‐controlled Phase 3 clinical study of the glucokinase activator PB ‐201 in treatment‐naive patients with type 2 diabetes mellitus: A study protocol . Diabetes, Obesity and Metabolism 25:3, pages 649-655.
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Ziyan Xie, Ting Xie, Jieying Liu, Qian Zhang & Xinhua Xiao. (2023) Glucokinase Inactivation Ameliorates Lipid Accumulation and Exerts Favorable Effects on Lipid Metabolism in Hepatocytes. International Journal of Molecular Sciences 24:5, pages 4315.
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Tobias Kroon, Therese Hagstedt, Ida Alexandersson, Annett FermMarie PeterssonStefanie Maurer, Bader ZarroukiKristina Wallenius, Nicholas D. OakesJeremie Boucher. (2022) Chronotherapy with a glucokinase activator profoundly improves metabolism in obese Zucker rats. Science Translational Medicine 14:668.
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Hilla Mills, Ronald Acquah, Nova Tang, Luke Cheung, Susanne Klenk, Ronald Glassen, Magali Pirson, Alain Albert, Duong Trinh Hoang & Thang Nguyen Van. (2022) Type 2 Diabetes Mellitus (T2DM) and Carbohydrate Metabolism in Relation to T2DM from Endocrinology, Neurophysiology, Molecular Biology, and Biochemistry Perspectives. Evidence-Based Complementary and Alternative Medicine 2022, pages 1-11.
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Ajmer Singh Grewal & Viney Lather. (2022) Small Molecule Allosteric Activators of Human Glucokinase for the Treatment of Type 2 Diabetes: Current Status and Challenges. Current Drug Discovery Technologies 19:4.
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Prateek Sharma, Sukhbir Singh, Neelam Sharma, Deepak Singla, Kumar Guarve & Ajmer Singh Grewal. (2022) Targeting human Glucokinase for the treatment of type 2 diabetes: an overview of allosteric Glucokinase activators. Journal of Diabetes & Metabolic Disorders 21:1, pages 1129-1137.
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Ana Karen Estrada, Timoteo Delgado-Maldonado, Edgar E. Lara-Ramírez, Ana Verónica Martínez-Vázquez, Eyra Ortiz-Pérez, Alma D. Paz-González, Debasish Bandyopadhyay & Gildardo Rivera. (2022) Recent Advances in the Development of Type 2 Sodium-Glucose Cotransporter Inhibitors for the Treatment of Type 2 Diabetes Mellitus. Mini-Reviews in Medicinal Chemistry 22:4, pages 586-599.
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Shinichiro Kawata, Akinobu Nakamura, Hideaki Miyoshi, Kelaier Yang, Ikumi Shigesawa, Yuki Yamauchi, Kazuhisa Tsuchida, Kazuno Omori, Kiyohiko Takahashi, Hiroshi Nomoto, Hiraku Kameda, Kyu Yong Cho, Yasuo Terauchi & Tatsuya Atsumi. (2021) Glucokinase activation leads to an unsustained hypoglycaemic effect with hepatic triglyceride accumulation in db/db mice . Diabetes, Obesity and Metabolism 24:3, pages 391-401.
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Akinobu Nakamura. (2022) Glucokinase as a therapeutic target based on findings from the analysis of mouse models. Endocrine Journal 69:5, pages 479-485.
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Akinobu Nakamura, Kazuno Omori & Yasuo Terauchi. (2021) Glucokinase activation or inactivation: Which will lead to the treatment of type 2 diabetes?. Diabetes, Obesity and Metabolism 23:10, pages 2199-2206.
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Saurabh C. Khadse, Nikhil D. Amnerkar, Krushna S. Dighole, Ashish M. Dhote, Vikas R. Patil, Deepak K. Lokwani, Vinod G. Ugale, Nitin B. Charbe & Vivekanand A. Chatpalliwar. (2020) Hetero-substituted sulfonamido-benzamide hybrids as glucokinase activators: Design, synthesis, molecular docking and in-silico ADME evaluation. Journal of Molecular Structure 1222, pages 128916.
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Brian E. Ford, Shruti S. Chachra, Ahmed Alshawi, Alfie Brennan, Suzannah Harnor, Celine Cano, David J. Baker, David M. Smith, Rebecca J. Fairclough & Loranne Agius. (2020) Chronic glucokinase activator treatment activates liver Carbohydrate response element binding protein and improves hepatocyte ATP homeostasis during substrate challenge . Diabetes, Obesity and Metabolism 22:11, pages 1985-1994.
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Zhiwei Zeng, Shi-Ying Huang & Tao Sun. (2020) Pharmacogenomic Studies of Current Antidiabetic Agents and Potential New Drug Targets for Precision Medicine of Diabetes. Diabetes Therapy 11:11, pages 2521-2538.
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Ping Wu, Zhenyu Liu, Xiaohong Jiang & Hao Fang. (2020) An Overview of Prospective Drugs for Type 1 and Type 2 Diabetes. Current Drug Targets 21:5, pages 445-457.
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Konstantinos A. Toulis, Krishnarajah Nirantharakumar, Chrysa Pourzitaki, Anthony H. Barnett & Abd A. Tahrani. (2020) Glucokinase Activators for Type 2 Diabetes: Challenges and Future Developments. Drugs 80:5, pages 467-475.
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Zachary Bloomgarden. (2019) Glucokinase and the potential of glucokinase activation in type 2 diabetes. Journal of Diabetes 11:8, pages 626-627.
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Timilehin David Oluwajuyitan & Oluwole Steve Ijarotimi. (2019) Nutritional, antioxidant, glycaemic index and Antihyperglycaemic properties of improved traditional plantain-based (Musa AAB) dough meal enriched with tigernut (Cyperus esculentus) and defatted soybean (Glycine max) flour for diabetic patients. Heliyon 5:4, pages e01504.
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Roberto de J. Sandoval-Muñíz, Belinda Vargas-Guerrero, Tereso J. Guzmán, Pedro M. García-López, Alma L. Martínez-Ayala, José A. Domínguez-Rosales & Carmen M. Gurrola-Díaz. (2018) Lupin gamma conglutin protein: effect on Slc2a2, Gck and Pdx-1 gene expression and GLUT2 levels in diabetic rats. Revista Brasileira de Farmacognosia 28:6, pages 716-723.
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Yue Ma, Risheka Ratnasabapathy, Chioma Izzi-Engbeaya, Marie-Sophie Nguyen-Tu, Errol Richardson, Sufyan Hussain, Ivan De Backer, Christopher Holton, Mariana Norton, Gaelle Carrat, Blanche Schwappach, Guy A. Rutter, Waljit S. Dhillo & James Gardiner. (2018) Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis. Diabetes, Obesity and Metabolism 20:9, pages 2246-2254.
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Hiroki Fujieda, Masakazu Kogami, Masao Sakairi, Noriyasu Kato, Mitsuhiro Makino, Naoki Takahashi, Toshiyuki Miyazawa, Satoko Harada & Tokuyuki Yamashita. (2018) Discovery of a potent glucokinase activator with a favorable liver and pancreas distribution pattern for the treatment of type 2 diabetes mellitus. European Journal of Medicinal Chemistry 156, pages 269-294.
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Brian Lu, Kiran Kurmi, Miguel Munoz-Gomez, Egon J. Jacobus Ambuludi, Jason M. Tonne, Kuntol Rakshit, Taro Hitosugi, Yogish C. Kudva, Aleksey V. Matveyenko & Yasuhiro Ikeda. (2018) Impaired β-cell glucokinase as an underlying mechanism in diet-induced diabetes. Disease Models & Mechanisms 11:6.
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Zhengyu Wang, Xiaofan Shi, Huan Zhang, Liang Yu, Yanhua Cheng, Hefeng Zhang, Huibin Zhang, Jinpei Zhou, Jing Chen, Xu Shen & Wenhu Duan. (2017) Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation. European Journal of Medicinal Chemistry 139, pages 128-152.
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Ziad H. Al-Oanzi, Sophia Fountana, Tabassum Moonira, Susan J. Tudhope, John L. Petrie, Ahmed Alshawi, Gillian Patman, Catherine Arden, Helen L. Reeves & Loranne Agius. (2017) Opposite effects of a glucokinase activator and metformin on glucose-regulated gene expression in hepatocytes. Diabetes, Obesity and Metabolism 19:8, pages 1078-1087.
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Mariela Glandt & Zachary Bloomgarden. 2017. Principles of Diabetes Mellitus. Principles of Diabetes Mellitus 999 1012 .
Mark F. McCarty. (2016) In type 1 diabetics, high-dose biotin may compensate for low hepatic insulin exposure, promoting a more normal expression of glycolytic and gluconeogenic enyzymes and thereby aiding glycemic control. Medical Hypotheses 95, pages 45-48.
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Loranne Agius. (2015) Dietary carbohydrate and control of hepatic gene expression: mechanistic links from ATP and phosphate ester homeostasis to the carbohydrate-response element-binding protein. Proceedings of the Nutrition Society 75:1, pages 10-18.
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Mariela Glandt & Zachary Bloomgarden. 2016. Principles of Diabetes Mellitus. Principles of Diabetes Mellitus 1 14 .

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