Quinapril treatment increases insulin-stimulated endothelial function and adiponectin gene expression in patients with type 2 diabetes.
OBJECTIVE
Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality and improve endothelial function in type 2 diabetic patients. We hypothesized that 2 months of quinapril treatment would improve insulin-stimulated endothelial function and glucose uptake in type 2 diabetic subjects and simultaneously increase the expression of genes that are pertinent for endothelial function and metabolism.


METHODS
Twenty-four type 2 diabetic subjects were randomized to receive 2 months of quinapril 20 mg daily or no treatment in an open parallel study. Endothelium-dependent and -independent vasodilation was studied during serotonin or sodium nitroprusside infusion in the diabetic patients and in 15 healthy subjects. Endothelial function, insulin-stimulated endothelial function, and insulin-stimulated glucose uptake were measured before and after quinapril treatment. Blood flow was measured by venous occlusion plethysmography. Gene expression was measured by real-time PCR.


RESULTS
Quinapril treatment increased insulin-stimulated endothelial function in the type 2 diabetic subjects (P = 0.005), whereas forearm glucose uptake was unchanged. Endothelial function was also increased by quinapril (P = 0.001). Systolic and diastolic blood pressures were reduced by quinapril (P < 0.001). Quinapril increased adiponectin gene expression in vascular tissue obtained from sc adipose biopsies.


CONCLUSIONS
Quinapril treatment increases insulin-stimulated endothelial function in patients with type 2 diabetes. Increased vascular adiponectin gene expression may contribute to this beneficial effect.
Hermann
Thomas S
TS
Department of Cardiology Y, Bispebjerg University Hospital, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark. th@heart.dk
Li
Weijie
W
Dominguez
Helena
H
Ihlemann
Nikolaj
N
Rask-Madsen
Christian
C
Major-Pedersen
Atheline
A
Nielsen
Dorthe Baunbjerg
DB
Hansen
Kaj Winther
KW
Hawkins
Meredith
M
Kober
Lars
L
Torp-Pedersen
Christian
C
D052242:Adiponectin / Q000235:genetics*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D003925:Diabetic Angiopathies / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D000077583:Quinapril; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*
D052242:Adiponectin; D000806:Angiotensin-Converting Enzyme Inhibitors; D017931:DNA Primers; D007004:Hypoglycemic Agents; D007328:Insulin; D044005:Tetrahydroisoquinolines; D000077583:Quinapril