Received: 4 January 2019 | Accepted: 14 February 2019 DOI: 10.1002/jcp.28412 REVIEW ARTICLE Wingless‐type inducible signaling pathway protein‐1 (WISP1) adipokine and glucose homeostasis Habib Yaribeygi 1 | Stephen L. Atkin 2 | Amirhossein Sahebkar 3,4,5 1 Chronic Kidney Disease Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2 Weill Cornell Medicine Qatar, Doha, Qatar 3 Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 4 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran 5 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Correspondence Amirhossein Sahebkar, Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran. Email: sahebkara@mums.ac.ir; amir_saheb2000@yahoo.com Habib Yaribeygi, PhD, Chronic Kidney Disease Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Email: habib.yari@yahoo.com Abstract Whilst the growing global prevalence of diabetes mellitus is a major healthcare problem, the exact pathophysiology of insulin resistance leading to diabetes mellitus remains unclear. Studies have confirmed that increased adiposity is linked to lower insulin sensitivity through the expression and release of adipocyte‐derived proteins such as adipokines. Wingless‐type (Wnt) inducible signaling pathway protein‐1 (WISP1) is a newly identified adipokine that has important roles in many molecular pathways and cellular events, with the suggestion that WISP1 adipokine is closely correlated to the progression of insulin resistance. Studies have shown that circulatory levels of WISP adipokine are higher in obese patients accompanied with increased insulin resistance. However, the exact role of WISP1 adipokine in the induction of insulin resistance is not completely understood. In this review, we detail the latest evidence showing that the WIPS1 adipokine impairs glucose homeostasis and induces diabetes mellitus. KEYWORDS adipokine, diabetes mellitus, glucose homeostasis, inflammation, insulin signaling, inducible signaling pathway protein‐1 (WISP1), wingless‐type (Wnt) 1 | INTRODUCTION The global prevalence of diabetes mellitus (DM) is growing rapidly (Collaboration, 2016). Estimations suggest that in 2050 upto 21% of US adults will develop DM (Boyle, Thompson, Gregg, Barker, & Williamson, 2010) that will reflect in the morbidity of diabetes complications, increased diabetes mortality, and a high healthcare burden (Association, 2013; Lopez‐Bastida, Boronat, Moreno, & Schurer, 2013). Diabetes related complications especially in the cardiovascular and renal systems are associated with an increased mortality rate in diabetes that may be reduced by good glycemic control (Lopez‐Bastida et al., 2013). Despite many suggested molecular mechanisms such as oxidative stress, inflammatory responses, insulin degradation, and beta cell failure, the exact pathophysiology of DM remains unclear (Yaribeygi, Farrokhi, Butler, & Sahebkar, 2018; Yaribeygi, Katsiki, Behnam, Iranpanah, & Sahebkar, 2018). In the recent decade, evidence has accumulated showing that adipocytes‐derived bioactive molecules known as "adipokines/ adipocytokines" may play important roles in the pathophysiology of insulin resistance and DM (Al‐Hamodi, Molham, Al‐Meeri, & Saif‐Ali, 2014; Cox et al., 2018). Adipokines are a class of proteins produced by adipose tissue and released into the circulation that are involved in many metabolic pathways and may act as a modulator, inducer, or inhibitor (Al‐Hamodi et al., 2014; Fasshauer & Blüher, 2015; Knights, Funnell, Pearson, Crossley, & Bell‐Anderson, 2014). Leptin was the first recognized adipokine in 1994, after which many more have been discovered (Conde et al., 2011). Wingless‐type (Wnt) inducible signaling pathway protein‐1 (WISP1) is a newly recognized adipokine that may play a dominant role in glucose homeostasis, as well as in the pathophysiology of DM (Jung et al., 2018; Murahovschi et al., 2015). It has been suggested that WISP1 adipokine may impair insulin signaling and modulates normal metabolic molecular pathways (Barchetta et al., 2017; Cimini et al., 2018; Jung et al., 2018). Studies have suggested that targeting adipokine signaling or expression may have promise for the design of new therapeutic strategies for diabetes and its complications (Jun & Lau, 2011). Therefore, in this current update, J Cell Physiol. 2019;1–5. wileyonlinelibrary.com/journal/jcp © 2019 Wiley Periodicals, Inc. | 1