Concentration dependence and time course of the effects of glucose on adenine and guanine nucleotides in mouse pancreatic islets.
Changes in the ATP:ADP ratio in pancreatic B cells may participate in the regulation of insulin secretion by glucose. Here, we have investigated the possible role of guanine nucleotides. Mouse islets were incubated in a control medium (when K+-ATP channels are the major site of regulation) or in a high K+ medium (when glucose modulates the effectiveness of cytosolic Ca2+ on exocytosis). Glucose induced a concentration-dependent (0-20 m) increase in GTP and a decrease in GDP in both types of medium, thus causing a progressive rise of the GTP:GDP ratio. ATP and ADP levels were 4-5-fold higher but varied in a similar way as those of guanine nucleotides. Insulin secretion was inversely correlated with ADP and GDP levels and positively correlated with the ATP:ADP and GTP:GDP ratios between 6 and 20 m glucose in control medium and between 0 and 20 m glucose in high K+ medium. The increases in the GTP:GDP and ATP:ADP ratios induced by a rise of glucose were faster than the decreases induced by a fall in glucose, but the changes of both ratios were again parallel. In conclusion, glucose causes large, concentration-dependent changes in guanine as well as in adenine nucleotides in islet cells. This raises the possibility that both participate in the regulation of nutrient-induced insulin secretion.
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Unité d'Endocrinologie et Métabolisme, University of Louvain, Faculty of Medicine, UCL 55.30, Avenue Hippocrate 55, B-1200 Brussels, Belgium.
Van den Berghe
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Henquin
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D000227:Adenine Nucleotides / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D015640:Ion Channel Gating; D007515:Islets of Langerhans / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D015221:Potassium Channels / Q000378:metabolism*
D000227:Adenine Nucleotides; D006150:Guanine Nucleotides; D007328:Insulin; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005947:Glucose