Zn-Fe primary battery-enabled controlled hydrogen release in stomach for improving insulin resistance in obesity-associated type 2 diabetes  

作　　者：Boyan Liu Peixun Lv Xiaoyi Zhang Chao Xia Xinru Liu Jingyu Liu Junli Xue Qianjun He Shucun Qin 

机构地区：[1]Key Laboratory of Major Diseases and Hydrogen Medical Translational Applications in Universities of Shandong Province&Key Laboratory of Hydrogen Biomedical Research of Health Commission of Shandong Province,Taishan Institute for Hydrogen Biomedical Research,The Second Affiliated Hospital of Shandong First Medical University,Tai’an,271000,China [2]Shanghai Key Laboratory of Hydrogen Science&Center of Hydrogen Science,School of Materials Science and Engineering,Shanghai Jiao Tong University,Shanghai,200240,China [3]School of Biomedical Engineering,Medical School,Shenzhen University,Shenzhen,518060,China [4]Shenzhen Research Institute,Shanghai Jiao Tong University,Shenzhen,518057,China

出　　处：《Bioactive Materials》2024年第3期242-250,共9页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China[82172078,81770855,82200508];Academic Promotion Programme of Shandong First Medical University[2019QL010];National Key Research and Development Program of China[2022YFB3804500];Shenzhen Science and Technology Program[RCJC20210706092010008].

摘　　要：Chronic systemic inflammation in obesity-associated type 2 diabetes (T2D) is a key inducing factor of insulin resistance (IR). Hydrogen molecule (H2) has been proved to be a safe and effective anti-inflammatory agent, but conventional H2 administration methods cannot provide a high dosage and a long duration of H2 treatment in IR-related tissues and thus lead to limited therapeutic efficacies. We here propose a new strategy of controlled H2 release to match the time window of gastric emptying for maximizing the bioavailability and therapeutic outcome of H2. This work enhances the hydrolysis rate of Zn by constructing a Zn-Fe primary-battery micro-/ nano-structure, and the H2-releasing rate is adjusted by tuning the ratio of Zn to Fe. The Zn-Fe micro-/nano-structure is orally administrated once daily to alleviate obesity-associated T2D in a leptin-deficient (ob/ob) mouse model. The H2 generation time of the Zn-Fe primary-battery micro-/nano-structure with the Fe/Zn ratio of 1:100 in gastric acid is about 3 h, just matching with the time window of gastric emptying in mice. In vivo monitoring results show that H2 generated by Zn-Fe micro-/nano-structure in stomach can effectively accumulate in major IR-sited tissues including liver, adipose tissue, and skeletal muscle at a high dose for a relatively long time compared to H2-rich water drinking. Oral administration of Zn-Fe micro-/nano-structure at 200 mg/kg body weight has realized an efficient IR improvement and remarkably ameliorated systemic inflammation in ob/ ob mice. In addition, a high-dose administration of Zn-Fe shows no visible toxicity in mice. This work provides a new strategy to maximize the outcome of hydrogen therapy.

关 键 词：Hydrogen therapy Primary battery Type 2 diabetes Insulin resistance ANTI-INFLAMMATION 

分 类 号：R587.1[医药卫生—内分泌]