Attenuated Purinergic Receptor Function in Patients With Type 2 Diabetes

Thaning, Pia; Bune, Laurids T.; Hellsten, Ylva; Pilegaard, Henriette; Saltin, Bengt; Rosenmeier, Jaya B.
January 2010
Diabetes;Jan2010, Vol. 59 Issue 1, p182
Academic Journal
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 P2Y2 and P2X1 receptors in skeletal muscles of diabetic subjects. RESEARCH DESIGN AND 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 (∼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/µmol ATP x kg, 494 ± 80 vs. 234 ± 39 ml/µmol UTP x kg, and 14.9 ± 2.7 vs. 7.5 ± 0.6 ml/µmol ADO x kg in control and diabetic subjects, respectively, thus malting 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. Diabetes 59:182-189, 2010


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