Attenuated purinergic receptor function in patients with type 2 diabetes.
OBJECTIVE
Extracellular nucleotides and nucleosides are involved in regulation of skeletal muscle blood flow. Diabetes induces cardiovascular dysregulation, but the extent to which the vasodilatatory capacity of nucleotides and nucleosides is affected in type 2 diabetes is unknown. The present study investigated 1) the vasodilatatory effect of ATP, uridine-triphosphate (UTP), and adenosine (ADO) and 2) the expression and distribution of P2Y(2) and P2X(1) receptors in skeletal muscles of diabetic subjects.


METHODS
In 10 diabetic patients and 10 age-matched control subjects, leg blood flow (LBF) was measured during intrafemoral artery infusion of ATP, UTP, and ADO, eliciting a blood flow equal to knee-extensor exercise at 12 W (approximately 2.6 l/min).


RESULTS
The vasodilatatory effect of the purinergic system was 50% lower in the diabetic group as exemplified by an LBF increase of 274 +/- 37 vs. 143 +/- 26 ml/micromol ATP x kg, 494 +/- 80 vs. 234 +/- 39 ml/micromol UTP x kg, and 14.9 +/- 2.7 vs. 7.5 +/- 0.6 ml/micromol ADO x kg in control and diabetic subjects, respectively, thus making the vasodilator potency as follows: UTP control subjects (100) > ATP control subjects (55) > UTP diabetic subjects (47) > ATP diabetic subjects (29) > ADO control subjects (3) > ADO diabetic subjects (1.5). The distribution and mRNA expression of receptors were similar in the two groups.


CONCLUSIONS
The vasodilatatory effect of the purinergic system is severely reduced in type 2 diabetic patients. The potency of nucleotides varies with the following rank order: UTP > ATP > ADO. This is not due to alterations in receptor distribution and mRNA expression, but may be due to differences in receptor sensitivity.
Thaning
Pia
P
Copenhagen Muscle Research Centre, Rigshospitalet, Denmark. piathaning@gmail.com
Bune
Laurids T
LT
Hellsten
Ylva
Y
Pilegaard
Henriette
H
Saltin
Bengt
B
Rosenmeier
Jaya B
JB
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000502:physiology; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D015444:Exercise; D005260:Female; D006801:Humans; D007866:Leg / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D058473:Receptors, Purinergic P2Y2; D012016:Reference Values; D012039:Regional Blood Flow / Q000502:physiology; D014544:Uridine Triphosphate / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
C546385:P2RY2 protein, human; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058473:Receptors, Purinergic P2Y2; D000255:Adenosine Triphosphate; D002784:Cholesterol; D000241:Adenosine; D014544:Uridine Triphosphate