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Vol 6, No 3 (2017)
REVIEW ARTICLES
Published online: 2017-09-29
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Role of purinergic signalling and proinflammatory cytokines in diabetes

Marek Cieślak, Michał Cieślak
DOI: 10.5603/DK.2017.0015
·
Clinical Diabetology 2017;6(3):90-100.

open access

Vol 6, No 3 (2017)
REVIEW ARTICLES
Published online: 2017-09-29

Abstract

 Extracellular purines activate P1 adenosine receptors and P2 nucleotide receptors. These receptors are pre­sent on the pancreatic islet cells as well as on hepato­cytes, adipocytes, pancreatic blood vessels and nerves. ATP is released together with insulin from b-cell gran­ules in response to a rapid decrease in blood glucose levels. The ATP-dependent P2X receptor activation on pancreatic b-cells results in a positive autocrine signal and subsequent insulin secretion. Adenosine, through activation of P1 receptors present on adipocytes and pancreatic islet cells, inhibits the release of insulin. Adenosine activates A2B receptors thereby stimulating production of IL-6 and other cytokines, which increases insulin resistance. Interleukin-6 also plays an important role in diabetes. In type 2 diabetes and obesity, the long-term increase of IL-6 concentration in blood above 5 pg/mL leads to the chronic and permanent increase in expression of SOCS3, contributing to the increase in insulin resistance in cells of the skeletal muscles, liver and adipose tissue. In diabetes there is an increased synthesis and release of pro-inflammatory cytokines, which cause the damage of the pancreatic islet cells, and in type 2 diabetes cause the development of insulin resistance. Ecto-enzymes metabolizing nucleotides are involved in the termination of the nucleotide signalling pathway and play the key role in regulation of extracel­lular ATP concentration. Ecto-NTPDases in cooperation with 5’-nucleotidase may significantly increase ecto-adenosine concentration. NTPDase3 activity has only been demonstrated on Langerhans cells. NTPDase3 may influence the secretion of insulin by hydrolysing adenine nucleotides. In diabetes the pro-inflammatory cytokines such as interleukin 1b (IL-1b), tumour ne­crosis factor-a (TNF-a) and interferon-g (IFN-g), as well as pancreatic derived factor PANDER are involved in the apoptosis of pancreatic b-cells. This causes distur­bance of the balance between pro-inflammatory and protective cytokines. We believe that neutralization of pro-inflammatory cytokines, especially interleukin 1b, with the IL-1 receptor antagonist (IL-1Ra) and/or IL-1b antibodies might cause the reduction of the inflamma­tory process in pancreas islets, normalize concentration of glucose in blood and decrease the insulin resistance. (Clin Diabetol 2017; 6, 3: 90–100)

Abstract

 Extracellular purines activate P1 adenosine receptors and P2 nucleotide receptors. These receptors are pre­sent on the pancreatic islet cells as well as on hepato­cytes, adipocytes, pancreatic blood vessels and nerves. ATP is released together with insulin from b-cell gran­ules in response to a rapid decrease in blood glucose levels. The ATP-dependent P2X receptor activation on pancreatic b-cells results in a positive autocrine signal and subsequent insulin secretion. Adenosine, through activation of P1 receptors present on adipocytes and pancreatic islet cells, inhibits the release of insulin. Adenosine activates A2B receptors thereby stimulating production of IL-6 and other cytokines, which increases insulin resistance. Interleukin-6 also plays an important role in diabetes. In type 2 diabetes and obesity, the long-term increase of IL-6 concentration in blood above 5 pg/mL leads to the chronic and permanent increase in expression of SOCS3, contributing to the increase in insulin resistance in cells of the skeletal muscles, liver and adipose tissue. In diabetes there is an increased synthesis and release of pro-inflammatory cytokines, which cause the damage of the pancreatic islet cells, and in type 2 diabetes cause the development of insulin resistance. Ecto-enzymes metabolizing nucleotides are involved in the termination of the nucleotide signalling pathway and play the key role in regulation of extracel­lular ATP concentration. Ecto-NTPDases in cooperation with 5’-nucleotidase may significantly increase ecto-adenosine concentration. NTPDase3 activity has only been demonstrated on Langerhans cells. NTPDase3 may influence the secretion of insulin by hydrolysing adenine nucleotides. In diabetes the pro-inflammatory cytokines such as interleukin 1b (IL-1b), tumour ne­crosis factor-a (TNF-a) and interferon-g (IFN-g), as well as pancreatic derived factor PANDER are involved in the apoptosis of pancreatic b-cells. This causes distur­bance of the balance between pro-inflammatory and protective cytokines. We believe that neutralization of pro-inflammatory cytokines, especially interleukin 1b, with the IL-1 receptor antagonist (IL-1Ra) and/or IL-1b antibodies might cause the reduction of the inflamma­tory process in pancreas islets, normalize concentration of glucose in blood and decrease the insulin resistance. (Clin Diabetol 2017; 6, 3: 90–100)

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Keywords

diabetes mellitus, nucleotides, adenosine, purinergic receptors, ecto-nucleotidases, proinflammatory cytokines.

About this article
Title

Role of purinergic signalling and proinflammatory cytokines in diabetes

Journal

Clinical Diabetology

Issue

Vol 6, No 3 (2017)

Pages

90-100

Published online

2017-09-29

DOI

10.5603/DK.2017.0015

Bibliographic record

Clinical Diabetology 2017;6(3):90-100.

Keywords

diabetes mellitus
nucleotides
adenosine
purinergic receptors
ecto-nucleotidases
proinflammatory cytokines.

Authors

Marek Cieślak
Michał Cieślak

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