Perivascular Adipose Tissue Control of Insulin-Induced Vasoreactivity in Muscle Is Impaired in db/db Mice

  1. Etto C. Eringa2
  1. 1Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
  2. 2Laboratory for Physiology, VU University Medical Center, Amsterdam, the Netherlands
  3. 3Department of Medicine, University College London, London, U.K.
  4. 4INSERM, U1016, Cochin Institute, Paris, France
  5. 5Centre National de la Recherche Scientifique, UMR8104, Paris, France
  6. 6Paris Descartes University, Paris, France
  7. 7Department of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
  1. Corresponding author: Etto C. Eringa, e.eringa{at}vumc.nl.
  1. R.I.M. and W.B. contributed equally to this study.

Abstract

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 AMPKα2+/+ and AMPKα2−/− were studied. In AMPKα2−/− resistance arteries, insulin caused vasoconstriction in the presence of PVAT, and AMPKα2+/+ resistance arteries showed a neutral response. On the other hand, inhibition of the inflammatory kinase Jun NH2-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 AMPKα2 signaling. PVAT from obese mice inhibits insulin-induced vasodilation, which can be restored by inhibition of JNK.

  • Received November 16, 2011.
  • Accepted August 1, 2012.

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  1. Diabetes vol. 62 no. 2 590-598
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