Treatment of insulin resistance in obesity-associated type 2 diabetes mellitus through adiponectin gene therapy.
3T3-L1 Cells
Adiponectin
/ blood
Animals
Chitosan
/ administration & dosage
Diabetes Mellitus, Experimental
/ etiology
Diabetes Mellitus, Type 2
/ etiology
Genetic Therapy
Insulin Resistance
Male
Mice
Nanoparticles
/ administration & dosage
Obesity
/ complications
Oleic Acid
/ administration & dosage
Peptides
/ administration & dosage
Plasmids
Rats, Wistar
Adiponectin
Chitosan nanoparticles
Gene therapy
Insulin resistance
Type 2 diabetes mellitus
Journal
International journal of pharmaceutics
ISSN: 1873-3476
Titre abrégé: Int J Pharm
Pays: Netherlands
ID NLM: 7804127
Informations de publication
Date de publication:
15 Jun 2020
15 Jun 2020
Historique:
received:
09
01
2020
revised:
13
04
2020
accepted:
19
04
2020
pubmed:
26
4
2020
medline:
11
2
2021
entrez:
26
4
2020
Statut:
ppublish
Résumé
Global rise in obesity-associated type 2 diabetes mellitus (T2DM) has led to a major healthcare crisis. Development of efficient treatments to treat the underlying chronic inflammation in obesity-associated T2DM, is an unmet medical need. To this end, we have developed a plasmid adiponectin (pADN) based nanomedicine for the treatment of insulin resistance in type 2 diabetes mellitus. Adiponectin is a potent anti-inflammatory/anti-diabetic adipokine, which is downregulated in obesity. In this study, nanomicelles comprising chitosan conjugated to oleic acid and adipose homing peptide (AHP) were developed to deliver pADN to adipocytes. Cationic chitosan-oleic-AHP micelles were 112 nm in size, encapsulated 93% of pADN and protected gene cargo from DNase I mediated enzymatic degradation. In vitro, the nanomicellar formulation significantly increased adiponectin production compared to free plasmid as well as standard transfecting agent FuGENE®HD. Single dose subcutaneous administration of pADN-chitosan-oleic-AHP to obese-diabetic rats, resulted in improved insulin sensitivity for up to 6 weeks, which matched the glucose disposal ability of healthy rats. Serum adiponectin level in pADN-chitosan-oleic-AHP treated rats was comparable to healthy rats for up to 3 weeks post treatment. Overall, the results indicate that pADN-chitosan-oleic-AHP based therapy is a promising treatment approach for obesity-associated T2DM.
Identifiants
pubmed: 32334065
pii: S0378-5173(20)30341-0
doi: 10.1016/j.ijpharm.2020.119357
pmc: PMC7261390
mid: NIHMS1588605
pii:
doi:
Substances chimiques
Adiponectin
0
Peptides
0
Oleic Acid
2UMI9U37CP
Chitosan
9012-76-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
119357Subventions
Organisme : NIGMS NIH HHS
ID : R15 GM114701
Pays : United States
Informations de copyright
Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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