Attenuated purinergic receptor function in patients with type 2 diabetes

Area of Science:

• Cardiovascular Physiology
• Metabolic Disease Research
• Skeletal Muscle Biology

Background:

• Extracellular nucleotides and nucleosides regulate skeletal muscle blood flow.
• Diabetes mellitus is associated with cardiovascular dysregulation.
• The impact of type 2 diabetes on nucleotide-mediated vasodilation is not well understood.

Purpose of the Study:

• To investigate the vasodilatatory effects of adenosine triphosphate (ATP), uridine-triphosphate (UTP), and adenosine (ADO) in type 2 diabetic patients.
• To examine the expression and distribution of P2Y(2) and P2X(1) receptors in skeletal muscles of individuals with type 2 diabetes.

Main Methods:

• Leg blood flow (LBF) was measured in 10 type 2 diabetic patients and 10 age-matched controls.
• Intrafemoral artery infusions of ATP, UTP, and ADO were administered to elicit standardized blood flow.
• Skeletal muscle receptor expression and distribution were analyzed.

Main Results:

• The vasodilatatory response to ATP, UTP, and ADO was approximately 50% lower in diabetic subjects compared to controls.
• The vasodilator potency followed the order: UTP > ATP > ADO in both groups, but was significantly diminished in diabetics.
• Similar mRNA expression and distribution of P2Y(2) and P2X(1) receptors were observed between groups.

Conclusions:

• The vasodilatatory function of the purinergic system is significantly impaired in type 2 diabetes.
• The reduced efficacy is not attributable to altered receptor expression or distribution.
• Differences in receptor sensitivity may explain the diminished vasodilatory capacity in diabetic skeletal muscle.