Insulin action is associated with endothelial function in hypertension and type 2 diabetes.
A primary defect in the vascular action of insulin may be a key intermediate mechanism that links endothelial dysfunction with reduced insulin-mediated cellular glucose uptake in metabolic and cardiovascular disorders. The present study was designed to characterize more fully the relations between insulin action and endothelial function in male patients with essential hypertension (H, n=9) or type 2 diabetes (D, n=9) along with healthy control subjects (C) matched for age, body mass index, and lipid profile. They attended for measurement of whole-body insulin sensitivity (MCR) by the hyperinsulinemic clamp technique (day 1) and forearm vasoreactivity in response to intra-arterial infusions of insulin/glucose (day 2) and N(G)-monomethyl-L-arginine (L-NMMA) and norepinephrine (day 3) by bilateral venous-occlusion plethysmography. Results expressed as mean+/-SE MCR (mL/kg per minute) were 7.22+/-0. 99 (C), 6.32+/-0.78 (H), and 5.06+/-0.53 (D). Insulin/glucose-mediated vasodilation (IGMV) was 17.1+/-5.6% (C), 17. 2+/-5.5% (H), and 12.3+/-6.4% (D). L-NMMA vasoconstriction (LNV) was 37.9+/-5.1% (C), 37.5+/-2.3% (H), and 33.6+/-2.8% (D). There were no significant differences among groups for these parameters. Pooled correlation analyses revealed associations between MCR and IGMV (r=0. 46, P<0.05), MCR and LNV (r=0.44, P<0.05), and IGMV and LNV (r=0.52, P<0.01). This study supports functional coupling between insulin action (both metabolic and vascular) and basal endothelial nitric oxide production in humans.
Cleland
S J
SJ
Department of Medicine and Therapeutics, University of Glasgow, Glasgow, Scotland. scleand@clinmed.gla.ac.uk
Petrie
J R
JR
Small
M
M
Elliott
H L
HL
Connell
J M
JM
D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000008:administration & dosage; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D008076:Cholesterol, HDL; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D005947:Glucose; D009638:Norepinephrine