Absence of adenosine A1 receptors unmasks pulses of insulin release and prolongs those of glucagon and somatostatin.
OBJECTIVE
Extracellular ATP modulates pulsatile release of insulin, glucagon and somatostatin by activating P2Y(1) receptors. The present study examines if adenosine via A(1) receptors (A(1)R) interferes with pulsatile islet hormone release.


METHODS
Pancreas was perfused in mice expressing or lacking the A(1) receptor and the hormones measured with radioimmunoassay. Cytoplasmic Ca(2+) was recorded in isolated beta-cells using the fura-2 indicator.


RESULTS
Addition of 10 microM adenosine removed the Ca(2+) transients supposed to coordinate the insulin release pulses. This effect of adenosine was counteracted by 100 nM of the A(1)R antagonist DPCPX. In situ perfusion of the pancreas indicated two phases of islet hormone release when glucose was raised from 3.3 to 16.7 mM. The first phase was characterized by a brief dip followed by a peak, which was more pronounced for insulin and somatostatin than for glucagon. The second phase was markedly affected by knock out of A(1)R. The wild-type A(1)R (+/+) mice, usually lacked statistically verified insulin pulses but generated antisynchronous glucagon and somatostatin pulses with half-widths of 4 min. In the A(1)R (-/-) mice time-average release of insulin during the second phase was almost three times higher than in the controls and 30% of the hormone was released as distinct pulses with half-widths of 3 min. The absence of the A(1)R receptor resulted in 50% prolongation of the pulse cycles of glucagon and somatostatin and loss of their antisynchronous relationship.


CONCLUSIONS
The A(1)R receptor is important both for the amplitude (insulin) and duration (glucagon and somatostatin) of islet hormone pulses.
Salehi
Albert
A
Department of Clinical Science, CRC, University of Lund, Malmö, Sweden.
Parandeh
Fariborz
F
Fredholm
Bertil B
BB
Grapengiesser
Eva
E
Hellman
Bo
B
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D005934:Glucagon / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000235:genetics* / Q000502:physiology*; D013004:Somatostatin / Q000378:metabolism*
D007328:Insulin; D043682:Receptor, Adenosine A1; D013004:Somatostatin; D000255:Adenosine Triphosphate; D005934:Glucagon; D000241:Adenosine; D002118:Calcium