Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice
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Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice. / Meijer, Rick I; Bakker, Wineke; Alta, Caro-Lynn A F; Sipkema, Pieter; Yudkin, John S; Viollet, Benoit; Richter, Erik A.; Smulders, Yvo M; van Hinsbergh, Victor W M; Serné, Erik H; Eringa, Etto C.
I: Diabetes, Bind 62, Nr. 2, 2013, s. 590-598.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice
AU - Meijer, Rick I
AU - Bakker, Wineke
AU - Alta, Caro-Lynn A F
AU - Sipkema, Pieter
AU - Yudkin, John S
AU - Viollet, Benoit
AU - Richter, Erik A.
AU - Smulders, Yvo M
AU - van Hinsbergh, Victor W M
AU - Serné, Erik H
AU - Eringa, Etto C
N1 - CURIS 2013 NEXS 005
PY - 2013
Y1 - 2013
N2 - Microvascular recruitment in muscle is a determinant of insulin sensitivity. Whether perivascular adipose tissue (PVAT) is involved in disturbed insulin-induced vasoreactivity is unknown, as are the underlying mechanisms. This study investigates whether PVAT regulates insulin-induced vasodilation in muscle, the underlying mechanisms, and how obesity disturbs this vasodilation. Insulin-induced vasoreactivity of resistance arteries was studied with PVAT from C57BL/6 or db/db mice. PVAT weight in muscle was higher in db/db mice compared with C57BL/6 mice. PVAT from C57BL/6 mice uncovered insulin-induced vasodilation; this vasodilation was abrogated with PVAT from db/db mice. Blocking adiponectin abolished the vasodilator effect of insulin in the presence of C57BL/6 PVAT, and adiponectin secretion was lower in db/db PVAT. To investigate this interaction further, resistance arteries of AMPKa2(+/+) and AMPKa2(-/-) were studied. In AMPKa2(-/-) resistance arteries, insulin caused vasoconstriction in the presence of PVAT, and AMPKa2(+/+) resistance arteries showed a neutral response. On the other hand, inhibition of the inflammatory kinase Jun NH(2)-terminal kinase (JNK) in db/db PVAT restored insulin-induced vasodilation in an adiponectin-dependent manner. In conclusion, PVAT controls insulin-induced vasoreactivity in the muscle microcirculation through secretion of adiponectin and subsequent AMPKa2 signaling. PVAT from obese mice inhibits insulin-induced vasodilation, which can be restored by inhibition of JNK.
AB - Microvascular recruitment in muscle is a determinant of insulin sensitivity. Whether perivascular adipose tissue (PVAT) is involved in disturbed insulin-induced vasoreactivity is unknown, as are the underlying mechanisms. This study investigates whether PVAT regulates insulin-induced vasodilation in muscle, the underlying mechanisms, and how obesity disturbs this vasodilation. Insulin-induced vasoreactivity of resistance arteries was studied with PVAT from C57BL/6 or db/db mice. PVAT weight in muscle was higher in db/db mice compared with C57BL/6 mice. PVAT from C57BL/6 mice uncovered insulin-induced vasodilation; this vasodilation was abrogated with PVAT from db/db mice. Blocking adiponectin abolished the vasodilator effect of insulin in the presence of C57BL/6 PVAT, and adiponectin secretion was lower in db/db PVAT. To investigate this interaction further, resistance arteries of AMPKa2(+/+) and AMPKa2(-/-) were studied. In AMPKa2(-/-) resistance arteries, insulin caused vasoconstriction in the presence of PVAT, and AMPKa2(+/+) resistance arteries showed a neutral response. On the other hand, inhibition of the inflammatory kinase Jun NH(2)-terminal kinase (JNK) in db/db PVAT restored insulin-induced vasodilation in an adiponectin-dependent manner. In conclusion, PVAT controls insulin-induced vasoreactivity in the muscle microcirculation through secretion of adiponectin and subsequent AMPKa2 signaling. PVAT from obese mice inhibits insulin-induced vasodilation, which can be restored by inhibition of JNK.
U2 - 10.2337/db11-1603
DO - 10.2337/db11-1603
M3 - Journal article
C2 - 23048187
VL - 62
SP - 590
EP - 598
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 2
ER -
ID: 41813313