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

Abstract

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 Nonetheless, the commonly used anti-T2DM drugs failed to substant to treat T2DM when anti-T2DM was withdrawn.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.

• Authors: Xue Li, Mingming Zhen, Chen Zhou, Ruijun Deng, Tong Yu, Yingjie Wu, Chunying Shu, Chunru Wang, Chunli Bai
• Journal: ACS nano (ACS Nano) Vol. 13 Issue 8 Pg. 8597-8608 (08 27 2019) ISSN: 1936-086X [Electronic] United States
• PMID: 31314991 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fullerenes
• Glucose

Topics

• Animals
• Diabetes Mellitus, Experimental (drug therapy, metabolism, pathology)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism, pathology)
• Fullerenes (pharmacology)
• Glucose (metabolism)
• Humans
• Insulin Resistance (genetics)
• Liver (drug effects, metabolism, pathology)
• Mice
• Mice, Inbred NOD
• Pancreas (drug effects, metabolism, pathology)