PolyMet-HA nanocomplexs regulates glucose uptake by inhibiting SHIP2 activity.
J Biomater Appl
; 35(7): 849-856, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-32741295
ABSTRACT
Metformin, the first-line drug to treat type 2 diabetes, inhibits mitochondrial glycerolphosphate dehydrogenase in the liver to suppress gluconeogenesis. The major adverse effects caused by metformin were lactic acidosis and gastrointestinal discomfort. Therefore, there is need to develop a strategy with excellent permeability and appropriate retention effects.In this study, we synthesized a simple and biocompatible PolyMetformin (denoted as PolyMet) through conjugation of PEI1.8K with dicyandiamide, and then formed PolyMet-hyaluronic acid (HA) nanocomplexs by electrostatic self-assembly of the polycationic PolyMet and polyanionic hyaluronic acid (HA). Similar to metformin, the PolyMet-HA nanocomplexs could reduce the catalytic activity of the recombinant SHIP2 phosphatase domain in vitro. In SHIP2-overexpressing myotubes, PolyMet-HA nanocomplexes ameliorated glucose uptake by downregulating glucose transporter 4 endocytosis. PolyMet-HA nanocomplexes also could restore Akt signaling and protect the podocyte from apoptosis induced by SHIP2 overexpression. In essence, the PolyMet-HA nanocomplexes act similarly to metformin and increase glucose uptake, and maybe have a potential role in the treatment of type 2 diabetes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
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Nanomedicina
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Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases
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Glucose
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Metformina
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Biomater Appl
Assunto da revista:
ENGENHARIA BIOMEDICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China