Effect of Adenosine on the Morphological and Functional Integrity of Isolated Human Islets Exposed to Normoxic and Hypoxic Conditions.

Adenosine is a ubiquitous stress marker and is characterised by numerous vital functions in all organs. Although adenosine has been investigated for decades, the information about its metabolism in islet cells has mainly been obtained in rodents. The present study was undertaken to assess the effects of adenosine on isolated human islets when exposed to hypoxia. Isolated human islets were cultured in 1 or 5 mmol/L adenosine for 4-5 days at 1.5% oxygen. The postculture outcome was normalised to normoxia and 0 mmol/L adenosine. Whereas the mRNA expression of ADORA1, 2a, 2b and 3 in normoxia was unaffected by adenosine, hypoxia significantly increased the mRNA expression of these genes, which was further enhanced when islets were treated with adenosine. Hypoxia was the variable exerting the strongest impact, reducing islets' morphological and functional integrity. These parameters were improved by adding 1 mmol/L adenosine but deteriorated when using 5 mmol/L. The harmful effects of adenosine on islet apoptosis and total mortality were dose-dependent and present in all atmospheres. Islet characterisation clearly demonstrated that hypoxia is the main stressor that decreases islets' morphological and functional integrity. Further detailed studies are required to lock or unlock the different ADORA receptors and to identify their specific effects on islets' morphological and functional integrity.