Regulatory role of adenosine in insulin secretion from pancreatic β-cells--action via adenosine A₁ receptor and beyond.

Abstract

Under physiological conditions, insulin secretion from pancreatic β-cells is tightly regulated by different factors, including nutrients, nervous system, and other hormones. Pancreatic β-cells are also influenced by paracrine and autocrine interactions. The results of rodent studies indicate that adenosine is present within pancreatic islets and is implicated in the regulation of insulin secretion; however, effects depend on adenosine and glucose concentrations. Moreover, species differences in adenosine action were found. In rat islets, low adenosine was demonstrated to decrease glucose-induced insulin secretion and this effect is mediated via adenosine A1 receptor. In the presence of high adenosine concentrations, other mechanisms are activated and glucose-induced insulin secretion is increased. It is also well established that suppression of adenosine action increases insulin-secretory response of β-cells to glucose. In mouse islets, low adenosine concentrations do not significantly affect insulin secretion. However, in the presence of higher adenosine concentrations, potentiation of glucose-induced insulin secretion was demonstrated. It is also known that upon stimulation of insulin secretion, both rat and mouse islets release ATP. In rat islets, ATP undergoes extracellular conversion to adenosine. However, mouse islets are unable to convert extracellularly ATP to adenosine and adenosine arises from intracellular ATP degradation.