PMID: 9182705Jun 1, 1997Paper

Tight links between adenine and guanine nucleotide pools in mouse pancreatic islets: a study with mycophenolic acid

The Biochemical Journal
P DetimaryJ C Henquin

Abstract

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 microg/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 nucleo...Continue Reading

Citations

Sep 23, 2000·American Journal of Physiology. Endocrinology and Metabolism·S FujimotoY Seino
Nov 8, 2001·American Journal of Physiology. Cell Physiology·T D BatiukP C Dagher
Mar 20, 2014·Cell Biochemistry and Biophysics·Azadeh Meshkini
Nov 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Meritxell RoviraMichael J Parsons
Jun 12, 2002·The Journal of Cell Biology·Eric D SchwoebelMary Shannon Moore
Mar 15, 2011·Toxicology and Applied Pharmacology·Azadeh MeshkiniKazem Nouri
Sep 1, 2000·Seminars in Cell & Developmental Biology·J T DeeneyB E Corkey
Aug 16, 2005·Diabetes Research and Clinical Practice·Dai ShimonoYutaka Seino

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