Background: Insulin resistance is a major etiological factor in obesity, type 2 diabetes, and cardiovascular disease (CVD). Endothelial dysfunction may precede impairments in insulin-stimulated glucose uptake, thereby making it a key feature in development of CVD. However, the mechanism by which vascular tissue becomes dysfunctional is not clear. Summary: Extracellular vesicles (EVs) have emerged as potential mediators of insulin resistance and vascular dysfunction. EVs are membrane-bound particles released by tissues following cellular stress or activation. They carry “cargo” (e.g., insulin signaling proteins, eNOS-nitric oxide, and miRNA) that are believed to promote inter-cellular and interorgan communications. Herein, we review the underlying physiology of EVs in relation to type 2 diabetes and CVD risk. Specifically, we discuss how EVs may modulate metabolic (e.g., skeletal muscle, liver, and adipose) insulin sensitivity, and propose that EVs may modulate vascular insulin action to influence both endothelial function and arterial stiffness. We lastly identify how EVs may play a unique role following exercise to promote metabolic and vascular insulin sensitivity changes. Key Message: Gaining insight toward insulin-mediated EV mechanism has potential to identify novel pathways regulating cardiometabolic health and provide foundation for examining EVs as unique biomarkers and targets to prevent and/or treat chronic diseases.

1.
Abdul-Ghani
M
,
DeFronzo
RA
,
Del Prato
S
,
Chilton
R
,
Singh
R
,
Ryder
REJ
.
Erratum. Cardiovascular disease and type 2 diabetes: has the dawn of a new era arrived
.
Diabetes Care
.
2017
;
40
(
7
):
813
20
.
2.
Amabile
N
,
Guerin
AP
,
Tedgui
A
,
Boulanger
CM
,
London
GM
.
Predictive value of circulating endothelial microparticles for cardiovascular mortality in end-stage renal failure: a pilot study
.
Nephrol Dial Transplant
.
2012
;
27
(
5
):
1873
80
.
3.
Akhmerov
A
,
Parimon
T
.
Extracellular vesicles, inflammation, and cardiovascular disease
.
Cells
.
2022
:
11
.
4.
Nomura
S
.
Dynamic role of microparticles in type 2 diabetes mellitus
.
Curr Diabetes Rev
.
2009
;
5
(
4
):
245
51
.
5.
Giannella
A
,
Radu
CM
,
Franco
L
,
Campello
E
,
Simioni
P
,
Avogaro
A
, et al
.
Circulating levels and characterization of microparticles in patients with different degrees of glucose tolerance
.
Cardiovasc Diabetol
.
2017
;
16
(
1
):
118
.
6.
Amabile
N
,
Rautou
PE
,
Tedgui
A
,
Boulanger
CM
.
Microparticles: key protagonists in cardiovascular disorders
.
Semin Thromb Hemost
.
2010
;
36
(
8
):
907
16
.
7.
La Salvia
S
,
Gunasekaran
PM
,
Byrd
JB
,
Erdbrugger
U
.
Extracellular vesicles in essential hypertension: hidden messengers
.
Curr Hypertens Rep
.
2020
;
22
(
10
):
76
.
8.
Nozaki
T
,
Sugiyama
S
,
Sugamura
K
,
Ohba
K
,
Matsuzawa
Y
,
Konishi
M
, et al
.
Prognostic value of endothelial microparticles in patients with heart failure
.
Eur J Heart Fail
.
2010
;
12
(
11
):
1223
8
.
9.
Murakami
T
,
Horigome
H
,
Tanaka
K
,
Nakata
Y
,
Ohkawara
K
,
Katayama
Y
, et al
.
Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity
.
Thromb Res
.
2007
;
119
(
1
):
45
53
.
10.
Solomon
TP
,
Malin
SK
,
Karstoft
K
,
Haus
JM
,
Kirwan
JP
.
The influence of hyperglycemia on the therapeutic effect of exercise on glycemic control in patients with type 2 diabetes mellitus
.
JAMA Intern Med
.
2013
;
173
(
19
):
1834
6
.
11.
van der Pol
E
,
Sturk
A
,
van Leeuwen
T
,
Nieuwland
R
,
Coumans
F
,
ISTH-SSC-VB Working group
.
Standardization of extracellular vesicle measurements by flow cytometry through vesicle diameter approximation
.
J Thromb Haemost
.
2018
;
16
(
6
):
1236
45
.
12.
Ragland
TJ
,
Heiston
EM
,
Ballantyne
A
,
Stewart
NR
,
La Salvia
S
,
Musante
L
, et al
.
Extracellular vesicles and insulin-mediated vascular function in metabolic syndrome
.
Physiol Rep
.
2023
;
11
(
1
):
e15530
.
13.
Heiston
EM
,
Ballantyne
A
,
La Salvia
S
,
Musante
L
,
Erdbrugger
U
,
Malin
SK
.
Acute exercise decreases insulin-stimulated extracellular vesicles in conjunction with augmentation index in adults with obesity
.
J Physiol
.
2023
;
601
(
22
):
5033
50
.
14.
Thery
C
,
Witwer
KW
,
Aikawa
E
,
Alcaraz
MJ
,
Anderson
JD
,
Andriantsitohaina
R
, et al
.
Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
.
J Extracell Vesicles
.
2018
;
7
(
1
):
1535750
.
15.
Welsh
JA
,
Goberdhan
DCI
,
O’Driscoll
L
,
Buzas
EI
,
Blenkiron
C
,
Bussolati
B
, et al
.
Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches
.
J Extracell Vesicles
.
2024
;
13
(
2
):
e12404
.
16.
Santilli
F
,
Liani
R
,
Di Fulvio
P
,
Formoso
G
,
Simeone
P
,
Tripaldi
R
, et al
.
Increased circulating resistin is associated with insulin resistance, oxidative stress and platelet activation in type 2 diabetes mellitus
.
Thromb Haemost
.
2016
;
116
(
6
):
1089
99
.
17.
Nozaki
T
,
Sugiyama
S
,
Koga
H
,
Sugamura
K
,
Ohba
K
,
Matsuzawa
Y
, et al
.
Significance of a multiple biomarkers strategy including endothelial dysfunction to improve risk stratification for cardiovascular events in patients at high risk for coronary heart disease
.
J Am Coll Cardiol
.
2009
;
54
(
7
):
601
8
.
18.
Ridker
PM
,
Buring
JE
,
Rifai
N
,
Cook
NR
.
Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score
.
JAMA
.
2007
;
297
(
6
):
611
9
.
19.
DeFronzo
RA
,
Abdul-Ghani
M
.
Assessment and treatment of cardiovascular risk in prediabetes: impaired glucose tolerance and impaired fasting glucose
.
Am J Cardiol
.
2011
;
108
(
3 Suppl l
):
3B
24B
.
20.
Joseph
JJ
,
Deedwania
P
,
Acharya
T
,
Aguilar
D
,
Bhatt
DL
,
Chyun
DA
, et al
.
Comprehensive management of cardiovascular risk factors for adults with type 2 diabetes: a scientific statement from the American heart association
.
Circulation
.
2022
;
145
(
9
):
e722
59
.
21.
Vincent
MA
,
Clerk
LH
,
Lindner
JR
,
Price
WJ
,
Jahn
LA
,
Leong-Poi
H
, et al
.
Mixed meal and light exercise each recruit muscle capillaries in healthy humans
.
Am J Physiol Endocrinol Metab
.
2006
;
290
(
6
):
E1191
7
.
22.
Hallmark
R
,
Patrie
JT
,
Liu
Z
,
Gaesser
GA
,
Barrett
EJ
,
Weltman
A
.
The effect of exercise intensity on endothelial function in physically inactive lean and obese adults
.
PLoS One
.
2014
;
9
(
1
):
e85450
.
23.
Steinberg
HO
,
Chaker
H
,
Leaming
R
,
Johnson
A
,
Brechtel
G
,
Baron
AD
.
Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance
.
J Clin Invest
.
1996
;
97
(
11
):
2601
10
.
24.
Bastos-Amador
P
,
Perez-Cabezas
B
,
Izquierdo-Useros
N
,
Puertas
MC
,
Martinez-Picado
J
,
Pujol-Borrell
R
, et al
.
Capture of cell-derived microvesicles (exosomes and apoptotic bodies) by human plasmacytoid dendritic cells
.
J Leukoc Biol
.
2012
;
91
(
5
):
751
8
.
25.
Hugel
B
,
Martinez
MC
,
Kunzelmann
C
,
Freyssinet
JM
.
Membrane microparticles: two sides of the coin
.
Physiology
.
2005
;
20
:
22
7
.
26.
Eichner
NZM
,
Erdbrugger
U
,
Malin
SK
.
Extracellular vesicles: a novel target for exercise-mediated reductions in type 2 diabetes and cardiovascular disease risk
.
J Diabetes Res
.
2018
;
2018
:
7807245
.
27.
Barry
OP
,
Pratico
D
,
Lawson
JA
,
FitzGerald
GA
.
Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles
.
J Clin Invest
.
1997
;
99
(
9
):
2118
27
.
28.
Jansen
F
,
Yang
X
,
Franklin
BS
,
Hoelscher
M
,
Schmitz
T
,
Bedorf
J
, et al
.
High glucose condition increases NADPH oxidase activity in endothelial microparticles that promote vascular inflammation
.
Cardiovasc Res
.
2013
;
98
(
1
):
94
106
.
29.
Zhang
Y
,
Shi
L
,
Mei
H
,
Zhang
J
,
Zhu
Y
,
Han
X
, et al
.
Inflamed macrophage microvesicles induce insulin resistance in human adipocytes
.
Nutr Metab
.
2015
;
12
:
21
.
30.
Heiston
EM
,
Ballantyne
A
,
Stewart
NR
,
La Salvia
S
,
Musante
L
,
Lanningan
J
, et al
.
Insulin infusion decreases medium-sized extracellular vesicles in adults with metabolic syndrome
.
Am J Physiol Endocrinol Metab
.
2022
;
323
(
4
):
E378
88
.
31.
Freeman
DW
,
Noren Hooten
N
,
Eitan
E
,
Green
J
,
Mode
NA
,
Bodogai
M
, et al
.
Altered extracellular vesicle concentration, cargo, and function in diabetes
.
Diabetes
.
2018
;
67
(
11
):
2377
88
.
32.
Eichner
NZM
,
Gilbertson
NM
,
Musante
L
,
La Salvia
S
,
Weltman
A
,
Erdbrügger
U
, et al
.
An oral glucose load decreases postprandial extracellular vesicles in obese adults with and without prediabetes
.
Nutrients
.
2019
;
11
(
3
):
580
.
33.
Choi
Y
,
Kwon
Y
,
Kim
DK
,
Jeon
J
,
Jang
SC
,
Wang
T
, et al
.
Gut microbe-derived extracellular vesicles induce insulin resistance, thereby impairing glucose metabolism in skeletal muscle
.
Sci Rep
.
2015
;
5
:
15878
.
34.
Kranendonk
ME
,
de Kleijn
DP
,
Kalkhoven
E
,
Kanhai
DA
,
Uiterwaal
CSPM
,
van der Graaf
Y
, et al
.
Extracellular vesicle markers in relation to obesity and metabolic complications in patients with manifest cardiovascular disease
.
Cardiovasc Diabetol
.
2014
;
13
:
37
.
35.
Mleczko
J
,
Ortega
FJ
,
Falcon-Perez
JM
,
Wabitsch
M
,
Fernandez-Real
JM
,
Mora
S
.
Extracellular vesicles from hypoxic adipocytes and obese subjects reduce insulin-stimulated glucose uptake
.
Mol Nutr Food Res
.
2018
;
62
(
5
):
1700917
.
36.
Dotson
BL
,
Heiston
EM
,
Miller
SL
,
Malin
SK
.
Insulin stimulation reduces aortic wave reflection in adults with metabolic syndrome
.
Am J Physiol Heart Circ Physiol
.
2021
;
320
(
6
):
H2305
12
.
37.
Love
KM
,
Barrett
EJ
,
Malin
SK
,
Reusch
JEB
,
Regensteiner
JG
,
Liu
Z
.
Diabetes pathogenesis and management: the endothelium comes of age
.
J Mol Cell Biol
.
2021
;
13
(
7
):
500
12
.
38.
Burger
D
,
Schock
S
,
Thompson
CS
,
Montezano
AC
,
Hakim
AM
,
Touyz
RM
.
Microparticles: biomarkers and beyond
.
Clin Sci
.
2013
;
124
(
7
):
423
41
.
39.
Wang
JM
,
Su
C
,
Wang
Y
,
Huang
YJ
,
Yang
Z
,
Chen
L
, et al
.
Elevated circulating endothelial microparticles and brachial-ankle pulse wave velocity in well-controlled hypertensive patients
.
J Hum Hypertens
.
2009
;
23
(
5
):
307
15
.
40.
Amabile
N
,
Guignabert
C
,
Montani
D
,
Yeghiazarians
Y
,
Boulanger
CM
,
Humbert
M
.
Cellular microparticles in the pathogenesis of pulmonary hypertension
.
Eur Respir J
.
2013
;
42
(
1
):
272
9
.
41.
Lu
GY
,
Xu
RJ
,
Zhang
SH
,
Qiao
Q
,
Shen
L
,
Li
M
, et al
.
Alteration of circulatory platelet microparticles and endothelial microparticles in patients with chronic kidney disease
.
Int J Clin Exp Med
.
2015
;
8
(
9
):
16704
8
.
42.
Jahn
LA
,
Hartline
L
,
Rao
N
,
Logan
B
,
Kim
JJ
,
Aylor
K
, et al
.
Insulin enhances endothelial function throughout the arterial tree in healthy but not metabolic syndrome subjects
.
J Clin Endocrinol Metab
.
2016
;
101
(
3
):
1198
206
.
43.
Reynolds
LJ
,
Credeur
DP
,
Manrique
C
,
Padilla
J
,
Fadel
PJ
,
Thyfault
JP
.
Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1
.
J Appl Physiol
.
2017
;
122
(
1
):
38
47
.
44.
Yun
CH
,
Jung
KH
,
Chu
K
,
Kim
SH
,
Ji
KH
,
Park
HK
, et al
.
Increased circulating endothelial microparticles and carotid atherosclerosis in obstructive sleep apnea
.
J Clin Neurol
.
2010
;
6
(
2
):
89
98
.
45.
Esposito
K
,
Ciotola
M
,
Schisano
B
,
Gualdiero
R
,
Sardelli
L
,
Misso
L
, et al
.
Endothelial microparticles correlate with endothelial dysfunction in obese women
.
J Clin Endocrinol Metab
.
2006
;
91
:
3676
9
.
46.
Heiston
EM
,
Liu
Z
,
Ballantyne
A
,
Kranz
S
,
Malin
SK
.
A single bout of exercise improves vascular insulin sensitivity in adults with obesity
.
Obesity
.
2021
;
29
(
9
):
1487
96
.
47.
Horn
P
,
Cortese-Krott
MM
,
Amabile
N
,
Hundsdörfer
C
,
Kröncke
KD
,
Kelm
M
, et al
.
Circulating microparticles carry a functional endothelial nitric oxide synthase that is decreased in patients with endothelial dysfunction
.
J Am Heart Assoc
.
2012
;
2
(
1
):
e003764
.
48.
Martin
S
,
Tesse
A
,
Hugel
B
,
Martínez
MC
,
Morel
O
,
Freyssinet
JM
, et al
.
Shed membrane particles from T lymphocytes impair endothelial function and regulate endothelial protein expression
.
Circulation
.
2004
;
109
(
13
):
1653
9
.
49.
Ishida
K
,
Taguchi
K
,
Hida
M
,
Watanabe
S
,
Kawano
K
,
Matsumoto
T
, et al
.
Circulating microparticles from diabetic rats impair endothelial function and regulate endothelial protein expression
.
Acta Physiol (Oxf)
.
2016
;
216
(
2
):
211
20
.
50.
Good
ME
,
Musante
L
,
La Salvia
S
,
Howell
NL
,
Carey
RM
,
Le
TH
, et al
.
Circulating extracellular vesicles in normotension restrain vasodilation in resistance arteries
.
Hypertension
.
2020
;
75
(
1
):
218
28
.
51.
Burger
D
,
Turner
M
,
Xiao
F
,
Munkonda
MN
,
Akbari
S
,
Burns
KD
.
High glucose increases the formation and pro-oxidative activity of endothelial microparticles
.
Diabetologia
.
2017
;
60
(
9
):
1791
800
.
52.
Toth
EA
,
Turiak
L
,
Visnovitz
T
,
Cserép
C
,
Mázló
A
,
Sódar
BW
, et al
.
Formation of a protein corona on the surface of extracellular vesicles in blood plasma
.
J Extracell Vesicles
.
2021
;
10
(
11
):
e12140
.
53.
Oh
IY
,
Yoon
CH
,
Hur
J
,
Kim
JH
,
Kim
TY
,
Lee
CS
, et al
.
Involvement of E-selectin in recruitment of endothelial progenitor cells and angiogenesis in ischemic muscle
.
Blood
.
2007
;
110
(
12
):
3891
9
.
54.
Ross
MD
,
Wekesa
AL
,
Phelan
JP
,
Harrison
M
.
Resistance exercise increases endothelial progenitor cells and angiogenic factors
.
Med Sci Sports Exerc
.
2014
;
46
(
1
):
16
23
.
55.
Mendelsohn
ME
.
Protective effects of estrogen on the cardiovascular system
.
Am J Cardiol
.
2002
;
89
(
12A
):
12E
18E
; discussion 7E-8E.
56.
van der Pol
E
,
de Rond
L
,
Coumans
FAW
,
Gool
EL
,
Böing
AN
,
Sturk
A
, et al
.
Absolute sizing and label-free identification of extracellular vesicles by flow cytometry
.
Nanomedicine
.
2018
;
14
(
3
):
801
10
.
57.
Diehl
P
,
Fricke
A
,
Sander
L
,
Stamm
J
,
Bassler
N
,
Htun
N
, et al
.
Microparticles: major transport vehicles for distinct microRNAs in circulation
.
Cardiovasc Res
.
2012
;
93
(
4
):
633
44
.
58.
Abels
ER
,
Breakefield
XO
.
Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake
.
Cell Mol Neurobiol
.
2016
;
36
(
3
):
301
12
.
59.
Rautou
PE
,
Leroyer
AS
,
Ramkhelawon
B
,
Devue
C
,
Duflaut
D
,
Vion
AC
, et al
.
Microparticles from human atherosclerotic plaques promote endothelial ICAM-1-dependent monocyte adhesion and transendothelial migration
.
Circ Res
.
2011
;
108
(
3
):
335
43
.
60.
Faille
D
,
El-Assaad
F
,
Mitchell
AJ
,
Alessi
MC
,
Chimini
G
,
Fusai
T
, et al
.
Endocytosis and intracellular processing of platelet microparticles by brain endothelial cells
.
J Cell Mol Med
.
2012
;
16
:
1731
8
.
61.
Mulcahy
LA
,
Pink
RC
,
Carter
DR
.
Routes and mechanisms of extracellular vesicle uptake
.
J Extracell Vesicles
.
2014
;
3
(
1
).
62.
Zhang
M
,
Wang
L
,
Chen
Z
.
Research progress of extracellular vesicles in type 2 diabetes and its complications
.
Diabet Med
.
2022
;
39
(
9
):
e14865
.
63.
Bartel
DP
.
MicroRNAs: target recognition and regulatory functions
.
Cell
.
2009
;
136
(
2
):
215
33
.
64.
Foley
NH
,
O'Neill
LA
.
miR-107: a toll-like receptor-regulated miRNA dysregulated in obesity and type II diabetes
.
J Leukoc Biol
.
2012
;
92
(
3
):
521
7
.
65.
Jiang
LQ
,
Franck
N
,
Egan
B
,
Sjögren
RJO
,
Katayama
M
,
Duque-Guimaraes
D
, et al
.
Autocrine role of interleukin-13 on skeletal muscle glucose metabolism in type 2 diabetic patients involves microRNA let-7
.
Am J Physiol Endocrinol Metab
.
2013
;
305
(
11
):
E1359
66
.
66.
Vickers
KC
,
Landstreet
SR
,
Levin
MG
,
Shoucri
BM
,
Toth
CL
,
Taylor
RC
, et al
.
MicroRNA-223 coordinates cholesterol homeostasis
.
Proc Natl Acad Sci U S A
.
2014
;
111
(
40
):
14518
23
.
67.
Brennan
E
,
Wang
B
,
McClelland
A
,
Mohan
M
,
Marai
M
,
Beuscart
O
, et al
.
Protective effect of let-7 miRNA family in regulating inflammation in diabetes-associated atherosclerosis
.
Diabetes
.
2017
;
66
(
8
):
2266
77
.
68.
Massart
J
,
Sjogren
RJO
,
Lundell
LS
,
Mudry
JM
,
Franck
N
,
O'Gorman
DJ
, et al
.
Altered miR-29 expression in type 2 diabetes influences glucose and lipid metabolism in skeletal muscle
.
Diabetes
.
2017
;
66
(
7
):
1807
18
.
69.
Katayama
M
,
Wiklander
OPB
,
Fritz
T
,
Caidahl
K
,
El-Andaloussi
S
,
Zierath
JR
, et al
.
Circulating exosomal miR-20b-5p is elevated in type 2 diabetes and could impair insulin action in human skeletal muscle
.
Diabetes
.
2019
;
68
(
3
):
515
26
.
70.
Ying
W
,
Riopel
M
,
Bandyopadhyay
G
,
Dong
Y
,
Birmingham
A
,
Seo
JB
, et al
.
Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity
.
Cell
.
2017
;
171
(
2
):
372
84.e12
.
71.
Castano
C
,
Kalko
S
,
Novials
A
,
Parrizas
M
.
Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice
.
Proc Natl Acad Sci U S A
.
2018
;
115
(
48
):
12158
63
.
72.
Wu
G
,
Zhang
J
,
Fan
GG
,
Zou
ZY
,
Yin
YL
,
Li
GX
.
MiRNA-324-5p inhibits inflammatory response of diabetic vessels by targeting CPT1A
.
Eur Rev Med Pharmacol Sci
.
2020
;
24
:
12836
43
.
73.
Yang
JL
,
Han
NH
.
LncRNA UCA1 stimulates the repair of hyperglycemic vascular smooth muscle cells through targeting miR-582-5p
.
Eur Rev Med Pharmacol Sci
.
2020
;
24
:
12859
66
.
74.
de Gonzalo-Calvo
D
,
van der Meer
RW
,
Rijzewijk
LJ
,
Smit
JWA
,
Revuelta-Lopez
E
,
Nasarre
L
, et al
.
Serum microRNA-1 and microRNA-133a levels reflect myocardial steatosis in uncomplicated type 2 diabetes
.
Sci Rep
.
2017
;
7
(
1
):
47
.
75.
Veitch
S
,
Njock
MS
,
Chandy
M
,
Siraj
MA
,
Chi
L
,
Mak
H
, et al
.
MiR-30 promotes fatty acid beta-oxidation and endothelial cell dysfunction and is a circulating biomarker of coronary microvascular dysfunction in pre-clinical models of diabetes
.
Cardiovasc Diabetol
.
2022
;
21
(
1
):
31
.
76.
Chaturvedi
P
,
Kalani
A
,
Medina
I
,
Familtseva
A
,
Tyagi
SC
.
Cardiosome mediated regulation of MMP9 in diabetic heart: role of mir29b and mir455 in exercise
.
J Cell Mol Med
.
2015
;
19
(
9
):
2153
61
.
77.
Wang
X
,
Huang
W
,
Liu
G
,
Cai
W
,
Millard
RW
,
Wang
Y
, et al
.
Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells
.
J Mol Cell Cardiol
.
2014
;
74
:
139
50
.
78.
Wang
X
,
Gu
H
,
Huang
W
,
Peng
J
,
Li
Y
,
Yang
L
, et al
.
Hsp20-Mediated activation of exosome biogenesis in cardiomyocytes improves cardiac function and angiogenesis in diabetic mice
.
Diabetes
.
2016
;
65
(
10
):
3111
28
.
79.
Zhang
W
,
Wang
Y
,
Kong
Y
.
Exosomes derived from mesenchymal stem cells modulate miR-126 to ameliorate hyperglycemia-induced retinal inflammation via targeting HMGB1
.
Invest Ophthalmol Vis Sci
.
2019
;
60
(
1
):
294
303
.
80.
Satyadev
N
,
Rivera
MI
,
Nikolov
NK
,
Fakoya
AOJ
.
Exosomes as biomarkers and therapy in type 2 diabetes mellitus and associated complications
.
Front Physiol
.
2023
;
14
:
1241096
.
81.
Saez
T
,
Toledo
F
,
Sobrevia
L
.
Extracellular vesicles and insulin resistance: a potential interaction in vascular dysfunction
.
Curr Vasc Pharmacol
.
2019
;
17
(
5
):
491
7
.
82.
Dignat-George
F
,
Boulanger
CM
.
The many faces of endothelial microparticles
.
Arterioscler Thromb Vasc Biol
.
2011
;
31
(
1
):
27
33
.
83.
Leroyer
AS
,
Rautou
PE
,
Silvestre
JS
,
Castier
Y
,
Lesèche
G
,
Devue
C
, et al
.
CD40 ligand+ microparticles from human atherosclerotic plaques stimulate endothelial proliferation and angiogenesis a potential mechanism for intraplaque neovascularization
.
J Am Coll Cardiol
.
2008
;
52
(
16
):
1302
11
.
84.
Mezentsev
A
,
Merks
RM
,
O’Riordan
E
,
Chen
J
,
Mendelev
N
,
Goligorsky
MS
, et al
.
Endothelial microparticles affect angiogenesis in vitro: role of oxidative stress
.
Am J Physiol Heart Circ Physiol
.
2005
;
289
(
3
):
H1106
14
.
85.
Kim
HK
,
Song
KS
,
Chung
JH
,
Lee
KR
,
Lee
SN
.
Platelet microparticles induce angiogenesis in vitro
.
Br J Haematol
.
2004
;
124
(
3
):
376
84
.
86.
Yang
C
,
Mwaikambo
BR
,
Zhu
T
,
Gagnon
C
,
Lafleur
J
,
Seshadri
S
, et al
.
Lymphocytic microparticles inhibit angiogenesis by stimulating oxidative stress and negatively regulating VEGF-induced pathways
.
Am J Physiol Regul Integr Comp Physiol
.
2008
;
294
(
2
):
R467
76
.
87.
Formiga
FR
,
Pelacho
B
,
Garbayo
E
,
Abizanda
G
,
Gavira
JJ
,
Simon-Yarza
T
, et al
.
Sustained release of VEGF through PLGA microparticles improves vasculogenesis and tissue remodeling in an acute myocardial ischemia-reperfusion model
.
J Control Release
.
2010
;
147
(
1
):
30
7
.
88.
Fagerholm
S
,
Ortegren
U
,
Karlsson
M
,
Ruishalme
I
,
Stralfors
P
.
Rapid insulin-dependent endocytosis of the insulin receptor by caveolae in primary adipocytes
.
PLoS One
.
2009
;
4
(
6
):
e5985
.
89.
Mukherjee
S
,
Tessema
M
,
Wandinger-Ness
A
.
Vesicular trafficking of tyrosine kinase receptors and associated proteins in the regulation of signaling and vascular function
.
Circ Res
.
2006
;
98
(
6
):
743
56
.
90.
Ceriello
A
,
Motz
E
.
Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited
.
Arterioscler Thromb Vasc Biol
.
2004
;
24
(
5
):
816
23
.
91.
Bird
SR
,
Hawley
JA
.
Update on the effects of physical activity on insulin sensitivity in humans
.
BMJ Open Sport Exerc Med
.
2016
;
2
(
1
):
e000143
.
92.
Nystoriak
MA
,
Bhatnagar
A
.
Cardiovascular effects and benefits of exercise
.
Front Cardiovasc Med
.
2018
;
5
:
135
.
93.
Bruyndonckx
L
,
Hoymans
VY
,
De Guchtenaere
A
,
Van Helvoirt
M
,
Van Craenenbroeck
EM
,
Frederix
G
, et al
.
Diet, exercise, and endothelial function in obese adolescents
.
Pediatrics
.
2015
;
135
(
3
):
e653
61
.
94.
La Vignera
S
,
Condorelli
R
,
Vicari
E
,
D’Agata
R
,
Calogero
A
.
Aerobic physical activity improves endothelial function in the middle-aged patients with erectile dysfunction
.
Aging Male
.
2011
;
14
(
4
):
265
72
.
95.
Kim
JS
,
Kim
B
,
Lee
H
,
Thakkar
S
,
Babbitt
DM
,
Eguchi
S
, et al
.
Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells
.
Am J Physiol Heart Circ Physiol
.
2015
;
309
(
3
):
H425
33
.
96.
Kretzschmar
J
,
Babbitt
DM
,
Diaz
KM
,
Feairheller
DL
,
Sturgeon
KM
,
Perkins
AM
, et al
.
A standardized exercise intervention differentially affects premenopausal and postmenopausal African-American women
.
Menopause
.
2014
;
21
(
6
):
579
84
.
97.
Babbitt
DM
,
Diaz
KM
,
Feairheller
DL
,
Sturgeon
KM
,
Perkins
AM
,
Veerabhadrappa
P
, et al
.
Endothelial activation microparticles and inflammation status improve with exercise training in african americans
.
Int J Hypertens
.
2013
;
2013
:
538017
.
98.
Eichner
NZM
,
Gilbertson
NM
,
Heiston
EM
,
Musante
L
,
LA Salvia
S
,
Weltman
A
, et al
.
Interval exercise lowers circulating CD105 extracellular vesicles in prediabetes
.
Med Sci Sports Exerc
.
2020
;
52
(
3
):
729
35
.
99.
Chen
YC
,
Ho
CW
,
Tsai
HH
,
Wang
JS
.
Interval and continuous exercise regimens suppress neutrophil-derived microparticle formation and neutrophil-promoted thrombin generation under hypoxic stress
.
Clin Sci
.
2015
;
128
(
7
):
425
36
.
100.
Wang
JS
,
Chang
YL
,
Chen
YC
,
Tsai
HH
,
Fu
TC
.
Effects of normoxic and hypoxic exercise regimens on monocyte-mediated thrombin generation in sedentary men
.
Clin Sci
.
2015
;
129
(
4
):
363
74
.
101.
Powers
SK
,
Ji
LL
,
Kavazis
AN
,
Jackson
MJ
.
Reactive oxygen species: impact on skeletal muscle
.
Compr Physiol
.
2011
;
1
(
2
):
941
69
.
102.
Tushuizen
ME
,
Diamant
M
,
Heine
RJ
.
Postprandial dysmetabolism and cardiovascular disease in type 2 diabetes
.
Postgrad Med J
.
2005
;
81
(
951
):
1
6
.
103.
Cavalot
F
,
Pagliarino
A
,
Valle
M
,
Di Martino
L
,
Bonomo
K
,
Massucco
P
, et al
.
Postprandial blood glucose predicts cardiovascular events and all-cause mortality in type 2 diabetes in a 14-year follow-up: lessons from the San Luigi Gonzaga Diabetes Study
.
Diabetes Care
.
2011
;
34
(
10
):
2237
43
.
104.
Black
SE
,
Mitchell
E
,
Freedson
PS
,
Chipkin
SR
,
Braun
B
.
Improved insulin action following short-term exercise training: role of energy and carbohydrate balance
.
J Appl Physiol
.
2005
;
99
(
6
):
2285
93
.
105.
Newsom
SA
,
Everett
AC
,
Hinko
A
,
Horowitz
JF
.
A single session of low-intensity exercise is sufficient to enhance insulin sensitivity into the next day in obese adults
.
Diabetes Care
.
2013
;
36
(
9
):
2516
22
.
106.
Hanssen
H
,
Nussbaumer
M
,
Moor
C
,
Cordes
M
,
Schindler
C
,
Schmidt-Trucksass
A
.
Acute effects of interval versus continuous endurance training on pulse wave reflection in healthy young men
.
Atherosclerosis
.
2015
;
238
(
2
):
399
406
.
107.
Guiraud
T
,
Gayda
M
,
Juneau
M
,
Bosquet
L
,
Meyer
P
,
Théberge-Julien
G
, et al
.
A single bout of high-intensity interval exercise does not increase endothelial or platelet microparticles in stable, physically fit men with coronary heart disease
.
Can J Cardiol
.
2013
;
29
(
10
):
1285
91
.
108.
Chanda
M
,
Nantakomol
D
,
Suksom
D
,
Palasuwan
A
.
Cell-derived microparticles after exercise in individuals with G6PD Viangchan
.
Clin Hemorheol Microcirc
.
2015
;
60
(
2
):
241
51
.
109.
Mobius-Winkler
S
,
Hilberg
T
,
Menzel
K
,
Golla
E
,
Burman
A
,
Schuler
G
, et al
.
Time-dependent mobilization of circulating progenitor cells during strenuous exercise in healthy individuals
.
J Appl Physiol
.
2009
;
107
(
6
):
1943
50
.
110.
Rigamonti
AE
,
Bollati
V
,
Pergoli
L
,
Iodice
S
,
De Col
A
,
Tamini
S
, et al
.
Effects of an acute bout of exercise on circulating extracellular vesicles: tissue-sex-and BMI-related differences
.
Int J Obes
.
2020
;
44
(
5
):
1108
18
.
111.
Fruhbeis
C
,
Helmig
S
,
Tug
S
,
Simon
P
,
Kramer-Albers
EM
.
Physical exercise induces rapid release of small extracellular vesicles into the circulation
.
J Extracell Vesicles
.
2015
;
4
:
28239
.
112.
Whitham
M
,
Parker
BL
,
Friedrichsen
M
,
Hingst
JR
,
Hjorth
M
,
Hughes
WE
, et al
.
Extracellular vesicles provide a means for tissue crosstalk during exercise
.
Cell Metab
.
2018
;
27
(
1
):
237
51.e4
.
113.
Neuberger
EWI
,
Hillen
B
,
Mayr
K
,
Simon
P
,
Kramer-Albers
EM
,
Brahmer
A
.
Kinetics and topology of DNA associated with circulating extracellular vesicles released during exercise
.
Genes
.
2021
;
12
(
4
):
522
.
114.
Wilhelm
EN
,
Gonzalez-Alonso
J
,
Parris
C
,
Rakobowchuk
M
.
Exercise intensity modulates the appearance of circulating microvesicles with proangiogenic potential upon endothelial cells
.
Am J Physiol Heart Circ Physiol
.
2016
;
311
(
5
):
H1297
310
.
115.
Wahl
P
,
Wehmeier
UF
,
Jansen
FJ
,
Kilian
Y
,
Bloch
W
,
Werner
N
, et al
.
Acute effects of different exercise protocols on the circulating vascular microRNAs -16, -21, and -126 in trained subjects
.
Front Physiol
.
2016
;
7
:
643
.
116.
Salomon
C
,
Das
S
,
Erdbrugger
U
,
Kalluri
R
,
Kiang Lim
S
,
Olefsky
JM
, et al
.
Extracellular vesicles and their emerging roles as cellular messengers in endocrinology: an endocrine society scientific statement
.
Endocr Rev
.
2022
;
43
(
3
):
441
68
.
117.
Welsh
JA
,
Goberdhan
DC
,
O’Driscoll
L
,
Buzas
EI
, et al
.
Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced apporaches
.
J Extracell Vesicles
.
2023
;
13
(
2
):
e12404
.
You do not currently have access to this content.