The crosstalk between adenosine A2B receptor and insulin signalling in rat skeletal muscle cells
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ORIGINAL PAPER
The crosstalk between adenosine A2B receptor and insulin signalling in rat skeletal muscle cells Suna Habahbeh1 · Amer Imraish2 · Malek Zihlif1 Received: 8 April 2019 / Accepted: 28 June 2020 © Akadémiai Kiadó Zrt. 2020
Abstract Diabetes mellitus (DM) is a group of metabolic diseases characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action, or both. Insulin therapy might be affected by specific metabolic enzymes and transporters. There are conflicting reports in the literature on the role of adenosine receptor A2B (AR2B) in skeletal and cardiac muscle glucose metabolism. This study aims to find out if there is an association between AR2B and insulin signalling, especially the metabolic pathways (AKT-GSK). Differentiated L6 cell rat muscle cells were treated with insulin, adenosine agonist NECA, selective AR2B antagonist PSB 603 and combinations between these reagents, the expression of AKT2, GSK3α, and GSK3β were measured by qPCR hydrolysis probe technique. Insulin increases AKT2, GSK3α and GSK3β mRNA expression, while AR2B antagonist inhibits AKT2 GSK3α and GSK3β mRNA expression and combining AR2B antagonist with insulin diminish insulin action and decrease AKT2 GSK3α and GSK3β mRNA expression, which means a strong relationship between AR2B and insulin action. Furthermore AR2B agonist may be a good candidate as an anti-diabetic drug. Keywords Adenosine A2B receptors · Skeletal muscle · AKT and GSK
Introduction Adenosine is a crucial extracellular signalling molecule that is released from all of the cells, particularly under injury, inflammation and stress (St. Hilaire et al. 2009). Adenosine modulates many physiological processes in many aspects of tissue function by activating four subtypes of adenosine receptors (AR): AR1, AR2A, AR2B and AR3 (Haskó et al. 2009). Accumulative evidence shows that the adenosine and its receptors play a crucial role in glucose homoeostasis, insulin resistance and pathophysiology of type 2 diabetes mellitus (Novitskiy et al. 2008; Wojcik et al. 2014). Moreover, AR2B knockout mice showed insulin hyper-secretion as a result of high fat-diet and high glucose challenge suggesting an Suna Habahbeh and Amer Imraish contributed equally. * Malek Zihlif [email protected] 1
Department of Pharmacology, School of Medicine, The University of Jordan, Amman 11942, Jordan
Department of Biological Sciences, School of Science, The University of Jordan, Amman 11942, Jordan
2
endogenous effect of AR2B on increasing pancreatic secretion of insulin (Johnston-Cox et al. 2012). However, the molecular signalling of the adenosine system in glucose metabolism in skeletal muscle is not fully understood. Adenosine modulates a wide array of biological processes on many different tissues and organ systems, which suggests a potential effect in skeletal muscle regarding the glucose metabolism. Several studies have suggested that AR2B play a vital role in the maintenance of normal glucose homoeostasis (Novitskiy et al. 2008; Rüsing et al. 2006; Zablocki
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