Glucose metabolism in pancreatic B-cells leads to an increase in the ATP/ADP ratio that might participate in the regulation of insulin secretion. Good correlations have also been observed between guanine nucleotide levels in isolated pancreatic islets and insulin secretion. To assess whether guanine nucleotides have a specific role in stimulus–secretion coupling, their concentration should be modified selectively. This was attempted by culturing mouse islets overnight in the presence of mycophenolic acid (MPA), an inhibitor of GMP synthesis at the level of IMP dehydrogenase. The drug (25–50 μg/ml) did not affect the insulin content but decreased the GTP content of the islets and inhibited insulin secretion during subsequent incubation in the presence of 15 mM glucose. However, MPA also decreased the ATP/ADP ratio in the islets. The addition of guanine to the culture medium (to stimulate the salvage pathway of GTP synthesis) restored normal GTP levels, corrected the ATP/ADP ratio and partly prevented the inhibition of insulin release. In contrast, attempts to stimulate ATP synthesis specifically (by provision of adenine or adenosine) failed to reverse any of the effects of MPA. It is concluded that guanine and adenine nucleotide pools are tightly linked and cannot be specifically affected by MPA in pancreatic islet cells, probably because of the activity of nucleoside diphosphate kinase and because of the role of GTP in several reactions leading to adenine nucleotide generation. Contrary to previous claims, MPA is not an adequate tool for evaluating a specific role of guanine nucleotides in the control of insulin secretion.
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June 1997
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Research Article|
June 01 1997
Tight links between adenine and guanine nucleotide pools in mouse pancreatic islets: a study with mycophenolic acid
Philippe DETIMARY
;
Philippe DETIMARY
1Unit of Endocrinology and Metabolism, University of Louvain Faculty of Medicine, UCL 55.30, Avenue Hippocrate 55, B-1200 Brussels, Belgium
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Changqing XIAO
;
Changqing XIAO
1Unit of Endocrinology and Metabolism, University of Louvain Faculty of Medicine, UCL 55.30, Avenue Hippocrate 55, B-1200 Brussels, Belgium
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Jean-Claude HENQUIN
Jean-Claude HENQUIN
*
1Unit of Endocrinology and Metabolism, University of Louvain Faculty of Medicine, UCL 55.30, Avenue Hippocrate 55, B-1200 Brussels, Belgium
*To whom correspondence should be addressed.
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Biochem J (1997) 324 (2): 467–471.
Article history
Received:
December 18 1996
Revision Received:
January 27 1997
Accepted:
February 04 1997
Citation
Philippe DETIMARY, Changqing XIAO, Jean-Claude HENQUIN; Tight links between adenine and guanine nucleotide pools in mouse pancreatic islets: a study with mycophenolic acid. Biochem J 1 June 1997; 324 (2): 467–471. doi: https://doi.org/10.1042/bj3240467
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