PolyMet-HA nanocomplexs regulates glucose uptake by inhibiting SHIP2 activity.
J Biomater Appl
; 35(7): 849-856, 2021 02.
Article
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diabetes Mellitus, Type 2
/
Nanomedicine
/
Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
/
Glucose
/
Metformin
Limits:
Animals
/
Humans
Language:
En
Journal:
J Biomater Appl
Journal subject:
ENGENHARIA BIOMEDICA
Year:
2021
Document type:
Article
Affiliation country:
China