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Cerebrovascular actions of insulin
Author(s) -
Katakam Prasad V.G.,
Domoki Ferenc,
Lenti Laura,
Gaspar Tamas,
Snipes James A,
Busija David W
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.627.4
Subject(s) - vasodilation , medicine , vasoconstriction , endocrinology , insulin , insulin resistance , chemistry , calcium in biology , nitric oxide , calcium
Insulin resistance is a major risk factor for cerebrovascular and neurodegenerative diseases; however, cerebrovascular actions of insulin have not been studied. Therefore, we evaluated the vascular actions of insulin in isolated rat cerebral arteries (CAs). Diameter measurements of CAs showed a biphasic response to insulin; an initial constriction was followed by vasodilation. Endothelial denudation or large conductance calcium‐activated K + channels (K Ca ) inhibition resulted in vasoconstriction to insulin. Inhibition of small/intermediate conductance K Ca or inward‐rectifier or voltage gated or ATP dependent K + channels reduced insulin induced vasodilation. Inhibition of nitric oxide (NO) synthase or cytochrome P450 reduced vasodilation while inhibition of cyclooxygenase enhanced vasodilation to insulin. Inhibition of endothelin type A receptors enhanced the vasodilation while type B blockade diminished vasodilation to insulin. Inhibition of reactive oxygen species (ROS) production or scavenging the ROS abolished the vasoconstriction to insulin. Fluorescence studies of cultured rat cerebral microvascular endothelial cells showed elevation of intracellular calcium and enhanced generation of NO and ROS in response to insulin. Thus, insulin induced vasodilation was dependent K + channels and endothelial factors while vasoconstriction was mediated by ROS, prostanoids and endothelin.