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

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.

• Publication year

  2011

• Venue

  Physiological Research

• Publication date

  Unknown publication date

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.33549/PHYSIOLRES.932165PMID 21995904
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Purinergic receptors on insulin‐secreting cells

  1994influential reference
• Mechanisms by which glucose can control insulin release independently from its action on adenosine triphosphate-sensitive K+ channels in mouse B cells.

  1993cited by this paper
• Islet cell metabolism is reflected by the MTT (tetrazolium) colorimetric assay

  1992cited by this paper
• Cholinergic regulation of the endocrine pancreas.

  1990cited by this paper
• Effect of pertussis toxin on A1‐receptor‐mediated inhibition of insulin secretion

  1989cited by this paper
• Effects of extracellular adenine nucleotides on the electrical, ionic and secretory events in mouse pancreatic β‐cells

  1989cited by this paper
• Membrane and intracellular effects of adenosine in mouse pancreatic beta-cells.

  1989cited by this paper
• Comparison of the inhibition of insulin release by activation of adenosine and alpha 2-adrenergic receptors in rat beta-cells.

  1989influential reference
• Evidence for an inhibitory A1 subtype adenosine receptor on pancreatic insulin-secreting cells.

  1987influential reference
• Effects of adenosine, 2-deoxyadenosine and N6-phenylisopropyladenosine on rat islet function and metabolism.

  1982cited by this paper
• Studies on the local (paracrine) actions of glucagon, somatostatin and insulin in isolated islets of rat pancreas

  1980cited by this paper
• Adenosine and the regulation of insulin secretion by isolated rat islets of Langerhans.

  1977cited by this paper
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  1967cited by this paper

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• Insulin/adenosine axis linked signalling.

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  2014cites this paper
• Purinergic signalling in endocrine organs

  2014cites this paper
• Metabolic disturbances and defects in insulin secretion in rats with streptozotocin-nicotinamide-induced diabetes.

  2013cites this paper
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  2013influential citation