Chemokine Like Receptor-1 (CMKLR-1) Receptor: A Potential Therapeutic Target in Management of Chemerin Induced Type 2 Diabetes Mellitus and Cancer

Perumalsamy, Sangeetha; Zin, Nurul Ain Aqilah Mohd; Widodo, Riyanto Teguh; Ahmad, Wan Azman Wan; Vethakkan, Shireene Ratna; Huri, Hasniza Zaman

doi:10.2174/1381612823666170616081256

Cited by 41 publications

(29 citation statements)

References 87 publications

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“…Chemerin, a recently discovered adipokine [55] (also known as tazarotene-induced gene 2 (TIG2) and retinoic acid receptor responder 2 (RARRES2) [31]) is a 163 amino acid pre-proprotein that is secreted as a 143 amino acid (18 kDa) proprotein and subsequently undergoes C-terminal cleavage [32,33]. It has recently been discovered that chemerin has at least three receptors: G protein-coupled receptor CMKLR1 (chemokine-like receptor 1 or ChemR23), G protein-coupled receptor 1 (GPR1) and (C-C motif) receptor-like (CCRL) 2 [56][57][58]. CMKLR1 is expressed mainly in adipose tissue (higher levels in white compared to brown adipose tissue), bone, lung, brain, heart, and placenta [55,59].…”

Section: Discussionmentioning

confidence: 99%

“…Chemerin plays a role in adipogenesis [6,8,29,55,56,62], preadipocyte differentiation, adipocyte development and metabolism [29,31,57,[63][64][65], insulin sensitivity [6,56], and in lipid and glucose metabolism [29,55,58,66,67]. It is a pro-inflammatory agent [8,16,33,55,65], a chemoattractant for various types of cells [8,16,33,64,65], and modulates immune system function [31,56].…”

Section: Discussionmentioning

confidence: 99%

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Diabetes and Obesity—Cumulative or Complementary Effects On Adipokines, Inflammation, and Insulin Resistance

Sitar-Tăut

Coste

Ţărmure

et al. 2020

JCM

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Background: Diabetes and obesity are increasingly significant public health issues. The aim of this study was to evaluate the relationship between adipocytokines (leptin, ghrelin, and chemerin), inflammation (sVCAM1—soluble vascular adhesion molecule 1, sICAM1—soluble intercellular adhesion molecule 1), and insulin resistance in the presence of obesity and diabetes mellitus. Methods: 88 subjects, with a mean age of 61.96 ± 10.15 years, 75% of whom were women, were evaluated (in order to consider different associations between obesity and diabetes, subjects were categorized into four groups). Results: Overall, we found significant correlations between sICAM1-sVCAM1 rho = 0.426 and ghrelin-chemerin rho = −0.224. In the obesity + diabetes group, leptin correlated with sICAM1 rho = 0.786, and sVCAM1 negatively with glycemia/insulin rho = −0.85. Significant differences were found between the groups regarding sVCAM1 (p = 0.0134), leptin (p = 0.0265) and all insulin resistance scores, with differences influenced by the subjects’ gender. In conclusion, although there are currently many unknown aspects of the release and the role of various adipokines, in particular chemerin, its implication in early glucose metabolism dysregulation disorders seems very likely.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Diabetes and Obesity—Cumulative or Complementary Effects On Adipokines, Inflammation, and Insulin Resistance

Sitar-Tăut

Coste

Ţărmure

et al. 2020

JCM

View full text Add to dashboard Cite

show abstract

“…Beyond the lipid metabolism, chemerin also influences the dysregulation of glucose metabolism. Supporting the important roles of chemerin in systemic lipid and glucose metabolism, accumulating clinical data indicate that local and/or circulating chemerin levels are increased in patients with obesity, diabetes and cardiovascular disease ( Perumalsamy et al . 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Chemerin: a multifaceted adipokine involved in metabolic disorders

Helfer

2018

Journal of Endocrinology

242

208

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Metabolic syndrome is a global public health problem and predisposes individuals to obesity, diabetes and cardiovascular disease. Although the underlying mechanisms remain to be elucidated, accumulating evidence has uncovered a critical role of adipokines. Chemerin, encoded by the gene Rarres2, is a newly discovered adipokine involved in inflammation, adipogenesis, angiogenesis and energy metabolism. In humans, local and circulating levels of chemerin are positively correlated with BMI and obesity-related biomarkers. In this review, we discuss both peripheral and central roles of chemerin in regulating body metabolism. In general, chemerin is upregulated in obese and diabetic animals. Previous studies by gain or loss of function show an association of chemerin with adipogenesis, glucose homeostasis, food intake and body weight. In the brain, the hypothalamus integrates peripheral afferent signals including adipokines to regulate appetite and energy homeostasis. Chemerin increases food intake in seasonal animals by acting on hypothalamic stem cells, the tanycytes. In peripheral tissues, chemerin increases cell expansion, inflammation and angiogenesis in adipose tissue, collectively resulting in adiposity. While chemerin signalling enhances insulin secretion from pancreatic islets, contradictory results have been reported on how chemerin links to obesity and insulin resistance. Given the association of chemerin with obesity comorbidities in humans, advances in translational research targeting chemerin are expected to mitigate metabolic disorders. Together, the exciting findings gathered in the last decade clearly indicate a crucial multifaceted role for chemerin in the regulation of energy balance, making it a promising candidate for urgently needed pharmacological treatment strategies for obesity.

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“…However, to our knowledge, studies in humans examining the association between T2DM macroangiopathy and chemerin are lacking. Perumalsamy et al [13] reported that a high chemerin level in humans is considered a marker of insulin resistance (IR) and insulin storage, as well as of T2DM. Chemerin plays a role in both inflammation and metabolism and may provide a link between chronic inflammation and obesity and its related disorders.…”

Section: Introductionmentioning

confidence: 99%

Association of serum chemerin and inflammatory factors with type 2 diabetes macroangiopathy and waist-to-stature ratio

Yang

Zhou

et al. 2019

Bosn J of Basic Med Sci

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Chemerin is an adipocytokine that participates in glycolipid metabolism; however, its association with type 2 diabetes (T2DM) with lower extremity macroangiopathy (T2DM-V) has rarely been reported. This study explored the association of chemerin and inflammatory factors with body fat parameters, glucolipid metabolism, and insulin resistance (IR) in T2DM and T2DM-V. Patients were classified into normal glucose regulation (NGR), T2DM, and T2DM-V groups. Serum chemerin, glucolipid metabolic parameters, transforming growth factor (TGF)-β, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 and fasting insulin levels were measured along with HOMA-IR, body mass index (BMI), and waist-to-stature ratio (WSR). Serum chemerin, TGF-β, IL-6 and MCP-1 levels were significantly higher in T2DM groups than in NGR group, and BMI, WSR, fasting plasma glucose (FPG), 2hPG, glycated hemoglobin (HbA1c), triglycerides (TG) and HOMA-IR were higher in T2DM-V subgroups with moderate or severe lower extremity macroangiopathy than in NGR group, simple T2DM group, and T2DM-V subgroup with mild macroangiopathy. FPG, 2hPG, HbA1c, TG and HOMA-IR were higher in T2DM-V subgroup with severe macroangiopathy than in T2DM-V with moderate macroangiopathy (p < 0.05). In all groups, serum chemerin levels were positively correlated with BMI, WSR, FPG, 2hPG, HbA1c, fasting insulin, aspartate transaminase, TG, TGF-β, IL-6 and HOMA-IR (p < 0.05) and negatively correlated with high-density lipoprotein cholesterol [HDL-c] (p < 0.05). Multiple stepwise regression analysis showed that 2hPG, HbA1c, and HDL-c were independent predictors of serum chemerin levels (β = -0.768, -0.122, -0.115, and 3.261, respectively; p < 0.01). Collectively, chemerin, factors associated with obesity, pathological and physiological changes in glucolipid metabolism, and inflammatory factors may promote the development of T2DM macroangiopathy.

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Chemokine Like Receptor-1 (CMKLR-1) Receptor: A Potential Therapeutic Target in Management of Chemerin Induced Type 2 Diabetes Mellitus and Cancer

Abstract: Chemerin is one of the markers that may involve in development of both cancer and insulin resistance. Chemokine like receptor- 1 (CMKLR-1) receptor that regulates chemerin levels exhibits a potential therapeutic target for insulin resistance, type 2 diabetes and cancer treatment.

Cited by 41 publications

References 87 publications

Diabetes and Obesity—Cumulative or Complementary Effects On Adipokines, Inflammation, and Insulin Resistance

Diabetes and Obesity—Cumulative or Complementary Effects On Adipokines, Inflammation, and Insulin Resistance

Chemerin: a multifaceted adipokine involved in metabolic disorders

Association of serum chemerin and inflammatory factors with type 2 diabetes macroangiopathy and waist-to-stature ratio

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