Zhu JX, Pan ZN, Li D. Intracellular calcium channels: Potential targets for type 2 diabetes mellitus? World J Diabetes 2025; 16(4): 98995 [DOI: 10.4239/wjd.v16.i4.98995]
Corresponding Author of This Article
Dan Li, PhD, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, No. 18 Chaowang Road, Hangzhou 310014, Zhejiang Province, China. lidan@zjut.edu.cn
Research Domain of This Article
Biochemistry & Molecular Biology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Apr 15, 2025; 16(4): 98995 Published online Apr 15, 2025. doi: 10.4239/wjd.v16.i4.98995
Intracellular calcium channels: Potential targets for type 2 diabetes mellitus?
Jia-Xuan Zhu, Zhao-Nan Pan, Dan Li
Jia-Xuan Zhu, Zhao-Nan Pan, Dan Li, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, Zhejiang Province, China
Author contributions: Li D designed the topic; Li D and Zhu JX conducted the data collection; Li D, Zhu JX, and Pan ZN wrote manuscript; All authors have read and approved the final manuscript.
Supported by Calygene Biotechnology Inc., No. XT[2016]008@.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dan Li, PhD, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, No. 18 Chaowang Road, Hangzhou 310014, Zhejiang Province, China. lidan@zjut.edu.cn
Received: July 11, 2024 Revised: December 9, 2024 Accepted: January 23, 2025 Published online: April 15, 2025 Processing time: 231 Days and 23.7 Hours
Abstract
Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder. Despite the availability of numerous pharmacotherapies, a range of adverse reactions, including hypoglycemia, gastrointestinal discomfort, and lactic acidosis, limits their patient applicability and long-term application. Therefore, it is necessary to screen novel therapeutic drugs for T2DM treatment that have high efficacy but few adverse effects. AMP-activated protein kinase (AMPK) stands out as one of the most powerful targets for T2DM treatment. It can be activated through energy-sensing or calcium signaling. Medications that activate AMPK through the energy-sensing mechanism exhibit remarkable potency, but they are accompanied by lactic acidosis, carrying an alarmingly high mortality rate. Interestingly, medications that activate AMPK through calcium signaling, such as gliclazide, seldom induce lactic acidosis. However, the efficacy of gliclazide is much lower than metformin. Therefore, it is necessary to explore targets that activate AMPK via calcium signaling to avoid lactic acidosis while maintaining high potency. Ion channels are the main controller of intracellular calcium flow. Specific agonists and inhibitors targeting ion channels have been reported to activate AMPK. In this review, we will summarize the structure and function of calcium-permeable ion channels and discuss the potential of targeting these calcium channels for T2DM treatment.
Core Tip: The applicability and long-term use of drugs for type 2 diabetes mellitus (T2DM) treatment is limited due to their adverse effects. Drugs that activate AMP-activated protein kinase (AMPK) via calcium signaling exhibit fewer adverse effects such as lactic acidosis. However, the potency of these drugs is limited. Therefore, it is necessary to screen novel drugs with high efficacy but few adverse effects. The calcium channels control intracellular calcium flux, which could be potential targets for T2DM treatment via AMPK. This review summarizes 15 calcium channels, and discuss the potential of targeting these calcium channels for T2DM treatment.
