Effects of adenosine A 1 receptor antagonism on insulin secretion from rat pancreatic islets

Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Poznan, Poland.
Physiological research / Academia Scientiarum Bohemoslovaca (Impact Factor: 1.29). 12/2011; 60(6):905-11.
Source: PubMed


Adenosine is known to influence different kinds of cells, including beta-cells of the pancreas. However, the role of this nucleoside in the regulation of insulin secretion is not fully elucidated. In the present study, the effects of adenosine A(1) receptor antagonism on insulin secretion from isolated rat pancreatic islets were tested using DPCPX, a selective adenosine A(1) receptor antagonist. It was demonstrated that pancreatic islets stimulated with 6.7 and 16.7 mM glucose and exposed to DPCPX released significantly more insulin compared with islets incubated with glucose alone. The insulin-secretory response to glucose and low forskolin appeared to be substantially potentiated by DPCPX, but DPCPX was ineffective in the presence of glucose and high forskolin. Moreover, DPCPX failed to change insulin secretion stimulated by the combination of glucose and dibutyryl-cAMP, a non-hydrolysable cAMP analogue. Studies on pancreatic islets also revealed that the potentiating effect of DPCPX on glucose-induced insulin secretion was attenuated by H-89, a selective inhibitor of protein kinase A. It was also demonstrated that formazan formation, reflecting metabolic activity of cells, was enhanced in islets exposed to DPCPX. Moreover, DPCPX was found to increase islet cAMP content, whereas ATP was not significantly changed. These results indicate that adenosine A(1) receptor blockade in rat pancreatic islets potentiates insulin secretion induced by both physiological and supraphysiological glucose concentrations. This effect is proposed to be due to increased metabolic activity of cells and increased cAMP content.

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    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.
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