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Insulin‐mediated Venodilation is Impaired in Young, Healthy Carriers of the 825T Allele of the G‐protein β 3 Subunit Gene ( GNB3 )
Author(s) -
Mitchell Anna,
Pace Mutlu,
Nürnberger Jens,
Wenzel René R.,
Siffert Winfried,
Philipp Thomas,
Schäfers Rafael F.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.03.002
Subject(s) - medicine , phenylephrine , endocrinology , insulin , allele , vasodilation , nitric oxide synthase , insulin resistance , nitric oxide , biology , blood pressure , gene , biochemistry
Objective A C825T polymorphism has been identified for the gene encoding the G‐protein β 3 subunit ( GNB3 ). The 825T allele is associated with hypertension and obesity, which in turn are closely linked with resistance to the metabolic and vascular effects of insulin. We hypothesized that venodilation in response to insulin would be impaired in GNB3 825T‐allele carriers. Because vasodilatory properties of insulin are mainly mediated by nitric oxide, we also investigated the influence of the T−786C polymorphism of the gene for endothelial nitric oxide synthase ( NOS3 ) on insulin‐mediated venous responses. Methods We used the linear variable transducer technique to compare dorsal hand vein compliance in 31 young, healthy men ( GNB3 C825T: 15 CC, 14 CT, and 2 TT; NOS3 T−786C: 14 TT, 13 TC, and 4 CC). Individual dose‐response curves to phenylephrine (3.2–10,000 ng/min) were established, and veins were preconstricted by a constant infusion of phenylephrine at the individual dose needed to procure 70% of maximal constriction. Then insulin was infused (50–250,000 μU/min), and the changes in venous diameter were recorded. Results Venous response to insulin was biphasic, with venoconstriction at low doses being followed by venodilation at higher doses. Insulin dose‐response curves of GNB3 825T‐allele carriers were significantly shifted to the right (ANOVA, P < .001, versus CC). NOS3 T−786C‐allele carrier status had no influence on insulin‐induced vascular responses ( P = .60 for TC/CC versus TT). Conclusion This study is the first to show the influence of a genetic polymorphism on insulin‐mediated venodilation in men in vivo. Further studies are needed to determine whether these results translate to other vascular beds, and possible gender‐specific differences remain to be investigated. Clinical Pharmacology & Therapeutics (2005) 77 , 495–502; doi: 10.1016/j.clpt.2005.03.002