Gadofullerene Nanoparticles Reverse Dysfunctions of Pancreas and Improve Hepatic Insulin Resistance for Type 2 Diabetes Mellitus Treatment

被引:68
作者
Li, Xue [1 ,2 ]
Zhen, Mingming [1 ,2 ]
Zhou, Chen [1 ,2 ]
Deng, Ruijun [1 ,2 ]
Yu, Tong [1 ,2 ]
Wu, Yingjie [3 ]
Shu, Chunying [1 ,2 ]
Wang, Chunru [1 ,2 ]
Bai, Chunli [1 ,2 ]
机构
[1] Chinese Acad Sci, Beijing Natl Lab Mol Sci, Key Lab Mol Nanostruct & Nanotechnol, CAS Res Educ Ctr Excellence Mol Sci,Inst Chem, Beijing 100190, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[3] Dalian Med Univ, Inst Genome Engn Anim Models Human Dis, Dalian 116044, Peoples R China
关键词
gadofullerene nanoparticles; type 2 diabetes mellitus; pancreatic protection; insulin resistance; hepatic steatosis; TUMOR VASCULAR DISRUPTION; GLUCOSE; DRUGS; SECRETION; SULFONYLUREAS; HYPOGLYCEMIA; PATHOGENESIS; METFORMIN; AGENTS; RISK;
D O I
10.1021/acsnano.9b02050
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Type 2 diabetes mellitus (T2DM) has been one of the most prevalent metabolic disorders. Nonetheless, the commonly used anti-T2DM drugs failed to substant to treat T2DM when anti-T2DM was withdrawn. Here we put forward a superior and sustainable anti-diabetic strategy using intraperitoneal administration of amino-acid-functionalized gadofullerene nanoparticles (GFNPs) in db/db diabetic mice. Highly accumulated in the pancreas and liver, GFNPs could prominently decrease hyperglycemia, along with permanently maintaining normal blood sugar levels in T2DM mice and even stopping administration. Importantly, GFNPs reversed the pancreas islets dysfunctions by reducing oxidative stress and inflammation responses and fundamentally normalized the insulin secretory function of the pancreas islets. Mechanistically, GFNPs improved hepatic insulin resistance by regulating glucose and lipid metabolism through the activation of IRS2/PI3K/AKT signal pathways, resulting in inhibiting gluconeogenesis and increasing glycogenesis in the liver. Additionally, GFNPs relieved hepatic steatosis in the liver, ultimately maintaining systemic glucose and lipid metabolic homeostasis without obvious toxicity. Together, GFNPs reverse the dysfunctions of the pancreas and improve hepatic insulin resistance, providing a promising approach for T2DM treatment.
引用
收藏
页码:8597 / 8608
页数:12
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