PMID- 33460779
OWN - NLM
STAT- MEDLINE
DCOM- 20220103
LR  - 20220103
IS  - 1549-9642 (Electronic)
IS  - 1549-9634 (Linking)
VI  - 33
DP  - 2021 Apr
TI  - Improved insulin sensitivity in obese-diabetic mice via chitosan Nanomicelles 
      mediated silencing of pro-inflammatory Adipocytokines.
PG  - 102357
LID - S1549-9634(20)30211-2 [pii]
LID - 10.1016/j.nano.2020.102357 [doi]
AB  - Obesity induced chronic low-level inflammation is strongly associated with the 
      development of insulin resistance and progression of type-2 diabetes. Systemic 
      treatment with anti-inflammatory therapeutics requires high doses and is 
      associated with serious adverse effects owing to generalized suppression of the 
      immune system. Here we study localized knockdown of pro-inflammatory 
      adipocytokines in adipose tissue macrophages (ATMs) and adipocytes using RNA 
      interference for the treatment of insulin resistance. Chitosan nanomicelles 
      conjugated to ATM and adipocyte targeting ligands were used to transfect short 
      hairpin RNA (shRNA) against tumor necrosis factor-alpha (TNFalpha) and monocyte 
      chemoattractant protein-1 (MCP-1). Subcutaneous administration of 
      nanomicellar/pDNA polyplexes in obese-diabetic mice resulted in decreased 
      concentration of pro-inflammatory cytokines TNFalpha, MCP-1, IL-6, and IL-1beta along 
      with increased concentration of insulin-sensitizing adipokine adiponectin. 
      Downregulation of inflammatory cytokines resulted in improved insulin sensitivity 
      and glucose tolerance for up to six-weeks following single dose, compared to 
      untreated obese-diabetic mice.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Sharma, Divya
AU  - Sharma D
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, College of Health 
      Professions, North Dakota State University, Fargo, ND, USA.
FAU - Arora, Sanjay
AU  - Arora S
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, College of Health 
      Professions, North Dakota State University, Fargo, ND, USA.
FAU - Banerjee, Amrita
AU  - Banerjee A
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, College of Health 
      Professions, North Dakota State University, Fargo, ND, USA.
FAU - Singh, Jagdish
AU  - Singh J
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, College of Health 
      Professions, North Dakota State University, Fargo, ND, USA. Electronic address: 
      jagdish.singh@ndsu.edu.
LA  - eng
GR  - R15 GM114701/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210115
PL  - United States
TA  - Nanomedicine
JT  - Nanomedicine : nanotechnology, biology, and medicine
JID - 101233142
RN  - 0 (Adipokines)
RN  - 0 (Adiponectin)
RN  - 0 (Biocompatible Materials)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Insulin)
RN  - 0 (Micelles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9012-76-4 (Chitosan)
SB  - IM
MH  - Adipocytes/metabolism
MH  - Adipokines/*metabolism
MH  - Adiponectin/metabolism
MH  - Adipose Tissue/metabolism
MH  - Animals
MH  - Biocompatible Materials/chemistry
MH  - Chitosan/*chemistry/metabolism
MH  - Cytokines/metabolism
MH  - Diabetes Mellitus, Experimental
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Glucose Tolerance Test
MH  - Inflammation Mediators/metabolism
MH  - Insulin/*metabolism
MH  - Insulin Resistance/*physiology
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Micelles
MH  - Nanoparticles/*chemistry
MH  - Obesity/*metabolism
MH  - RAW 264.7 Cells
MH  - RNA Interference
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Chitosan nanomicelles
OT  - Inflammation
OT  - Insulin resistance
OT  - Obesity
OT  - RNA interference
EDAT- 2021/01/19 06:00
MHDA- 2022/01/04 06:00
CRDT- 2021/01/18 20:10
PHST- 2020/07/20 00:00 [received]
PHST- 2020/12/22 00:00 [revised]
PHST- 2020/12/22 00:00 [accepted]
PHST- 2021/01/19 06:00 [pubmed]
PHST- 2022/01/04 06:00 [medline]
PHST- 2021/01/18 20:10 [entrez]
AID - S1549-9634(20)30211-2 [pii]
AID - 10.1016/j.nano.2020.102357 [doi]
PST - ppublish
SO  - Nanomedicine. 2021 Apr;33:102357. doi: 10.1016/j.nano.2020.102357. Epub 2021 Jan 
      15.