Combined effect of adenosine,alpha adrenergic and adenosine antagonists on serum insulin and insulin secretion from rat pancreatic islets |
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| Institution: | 1. University of Washington, Seattle, WA;2. Seattle Children''s Hospital, Seattle, WA;3. Cystic Fibrosis Center, Children''s Hospital, University of Cologne;4. Faculty of Medicine and University Hospital Cologne, Cologne Germany;5. Case Western Reserve University School of Medicine, Cleveland, OH;6. National Heart & Lung Institute, Imperial College London, London, UK;7. Royal Brompton & Harefield NHS Foundation Trust, London, UK;8. Leeds Regional Paediatric Cystic Fibrosis Centre, Leeds, UK;9. Cystic Fibrosis Foundation, Bethesda, MD;10. University of Toronto, Toronto, Canada;11. Rainbow Babies and Children''s Hospital, Cleveland, OH;12. Children''s Health Research Centre, The University of Queensland, Brisbane, Australia;13. National Jewish Health, Denver, CO;14. University of Leuven, Leuven, Belgium;15. University of North Carolina at Chapel Hill, Chapel Hill, NC;p. Centre for Experimental Medicine, Queen''s University Belfast, Belfast, Northern Ireland;q. Medical University of South Carolina, Charleston, SC;r. Charles University, Prague, Czechia, Motol University Hospital, Prague, Czechia;s. Université de Paris, Paris, France;t. University of British Columbia, Vancouver, British Columbia |
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| Abstract: | - 1.1. The effect of adenosine separately or in combination with alpha-1 adrenergic antagonist prazosin and alpha-2 adrenergic antagonist yohimbine as well as adenosine antagonists 8-phenyltheophylline and xanthine amine conjugate on glucose-induced insulin secretion from isolated rat pancreatic islets was studied.
- 2.2. Their in vivo effects on serum glucose and insulin levels were also investigated. Adenosine at 10 and 100 μM inhibited significantly, insulin secretion from the isolated islets whereas at 10 mM slightly increased the secretion of insulin.
- 3.3. Prazosin used at 100 μM inhibited insulin secretion. When it combined with adenosine (10 μM) it augmented the inhibitory effect of adenosine.
- 4.4. In vivo prazosin (21 mg/kg bodywt) caused a hyperglycaemia which was accompanied by hypoinsulinaemia.
- 5.5. Concurrent administration of this drug with adenosine neither affect the hyperglycaemic nor the hypoinsulinaemic effects of adenosine.
- 6.6. On the other hand, yohimbine (100 μM) has no effect neither separately nor in combination with adenosine (10 μM) in modulating the inhibitory effect of adenosine on insulin secretion.
- 7.7. When Yohimbine administered at 19.5 mg/kg body wt it did not alter serum glucose but it markedly increased the serum insulin level. Its combined administration with adenosine reduced the hyperglycaemic effect of adenosine with a remarkable increase in serum insulin.
- 8.8. Both adenosine-antagonists were ineffective in alteration of insulin secretion.
- 9.9. However, combination of 8-phenyltheophylline with adenosine (10 μM) totally blocked the inhibitory effect of adenosine on insulin secretion while xanthine amine conjugate failed to prevent this effect of adenosine.
- 10.10. These results indicate that the inhibitory effect of adenosine on insulin secretion is neither mediated via alpha-1 nor alpha-2 adrenoceptors. It might be via activation of specific adenosine receptors on rat islets which are sensitive to blockade by 8-phenyltheophylline.
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