Prokineticin receptor 1 ameliorates insulin resistance in skeletal muscle

Mok, Jongsoo; Park, Tae Sub; Kim, Sunhong; Kim, Daehoon; Choi, Cheol Soo; Park, Joonghoon

doi:10.1096/fj.202001641r

Cited by 10 publications

(9 citation statements)

References 44 publications

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“…As shown in Figure , 2 μg/mL collagen‐stimulated platelet aggregation and rate of aggregation were significantly impaired by the addition of 50 nM IL32. By contrast, 2 µg/mL collagen‐stimulated platelet aggregation was not affected by the addition of PROK2 at a concentration of 10 nM ( Figure ), representing ~ 10 to 50‐fold the half‐maximal effective concentration of this cytokine in in vitro assays 31,32 . Moreover, the addition of PROK2 alone to washed platelets did not lead to appreciable aggregation ( Figure ).…”

Section: Resultsmentioning

confidence: 95%

Differences in the Platelet mRNA Landscape Portend Racial Disparities in Platelet Function and Suggest Novel Therapeutic Targets

Garofano

Park

Alarcón

et al. 2021

Clin Pharma and Therapeutics

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The African American (AA) population displays a 1.6 to 3‐fold higher incidence of thrombosis and stroke mortality compared with European Americans (EAs). Current antiplatelet therapies target the ADP‐mediated signaling pathway, which displays significant pharmacogenetic variation for platelet reactivity. The focus of this study was to define underlying population differences in platelet function in an effort to identify novel molecular targets for future antiplatelet therapy. We performed deep coverage RNA‐Seq to compare gene expression levels in platelets derived from a cohort of healthy volunteers defined by ancestry determination. We identified > 13,000 expressed platelet genes of which 480 were significantly differentially expressed genes (DEGs) between AAs and EAs. DEGs encoding proteins known or predicted to modulate platelet aggregation, morphology, or platelet count were upregulated in AA platelets. Numerous G‐protein coupled receptors, ion channels, and pro‐inflammatory cytokines not previously associated with platelet function were likewise differentially expressed. Many of the signaling proteins represent potential pharmacologic targets of intervention. Notably, we confirmed the differential expression of cytokines IL32 and PROK2 in an independent cohort by quantitative real‐time polymerase chain reaction, and provide functional validation of the opposing actions of these two cytokines on collagen‐induced AA platelet aggregation. Using Genotype‐Tissue Expression whole blood data, we identified 516 expression quantitative trait locuses with Fst values > 0.25, suggesting that population‐differentiated alleles may contribute to differences in gene expression. This study identifies gene expression differences at the population level that may affect platelet function and serve as potential biomarkers to identify cardiovascular disease risk. Additionally, our analysis uncovers candidate novel druggable targets for future antiplatelet therapies.

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Section: Resultsmentioning

confidence: 95%

Differences in the Platelet mRNA Landscape Portend Racial Disparities in Platelet Function and Suggest Novel Therapeutic Targets

Garofano

Park

Alarcón

et al. 2021

Clin Pharma and Therapeutics

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“…AVPR1A expression is increased in failing hearts, and overexpression of AVPR1A in a mouse model has been shown to impair cardiac function (51). Other GPCRs with remarkable expression profiles include orphan GPCR (GPR35) (52), Prokineticin Receptor 1 (PROKR1) (53), LGR4 (54)(55), and Adhesion G Protein-Coupled Receptor F5 (AD-GRF5) (56). Previous studies have suggested that these GPCRs may play a critical role in controlling adipocyte biology and systemic energy homeostasis but more work is needed for a detailed understanding of their functional significance in adipose tissue metabolism.…”

Section: Discussionmentioning

confidence: 99%

Profiling of G-protein Coupled Receptors in Adipose Tissue and Differentiating Adipocytes Offers a Translational Resource for Obesity/Metabolic Research

Mahri¹,

Okla²,

Rashid³

et al. 2022

Preprint

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G protein-coupled receptors (GPCRs) are expressed essentially on all cells, facilitating cellular responses to external stimuli, and are involved in nearly every biological process. Several members of this family play significant roles in the regulation of adipogenesis and adipose me-tabolism. However, the expression and functional significance of a vast number of GPCRs in adipose tissue are unknown. We used a high-throughput RT-PCR panel to determine the expres-sion of the entire repertoire of non-sensory GPCRs in mouse white, and brown adipose tissue and assess changes in their expression during adipogenic differentiation of murine adipocyte cell line, 3T3-L1. In addition, the expression of GPCRs in subcutaneous adipose tissues from lean, obese, and diabetic human subjects was evaluated by re-analyzing RNA-sequencing data. We detected a total of 292 and 271 GPCRs in mouse white and brown adipose tissue, respectively. There is a significant overlap in the expression of GPCRs between the two adipose tissue depots but several GPCRs are specifically expressed in one of the two tissue types. Adipogenic differ-entiation of 3T3-L1 cells had a profound impact on the expression of several GPCRs. RNA se-quencing of subcutaneous adipose from healthy human subjects detected 255 GPCRs and obesity significantly changed the expression of several GPCRs in adipose tissue. Finally, we report sev-eral highly expressed GPCRs with no known role in adipose biology whose expression was sig-nificantly altered during adipogenic differentiation and/or in the diseased human subjects. These GPCRs could play an important role in adipose metabolism and serve as a valuable translational resource for obesity and metabolic research.

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“…Skeletal muscle is the primary and largest site for modulating normal glucose concentrations in the postprandial state in humans. More than 80% of glucose uptake activity is mainly regulated in skeletal muscle under euglycemic hyperinsulinemic conditions [58,59]. In skeletal muscle, insulin binds to the insulin receptor, which leads to activation of PI3K and an increase in the level of intracellular PIP 3 .…”

Section: Role Of Pi3k/akt In Muscle Tissuementioning

confidence: 99%

“…In skeletal muscle, insulin binds to the insulin receptor, which leads to activation of PI3K and an increase in the level of intracellular PIP 3 . The PIP 3 activates AKT2 at the plasma membrane, which is necessary for subsequent glucose uptake into the skeletal muscle through GLUT4 membrane translocation [59,60]. Incorporated glucose is converted to glycogen for storage or enters the glycolytic pathway where it is oxidized for energy production [61].…”

Section: Role Of Pi3k/akt In Muscle Tissuementioning

confidence: 99%

Targeting PI3K/AKT signaling pathway in obesity

Savova

Mihaylova

Tews

et al. 2023

Biomedicine & Pharmacotherapy

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Prokineticin receptor 1 ameliorates insulin resistance in skeletal muscle

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 10 publications

References 44 publications

Differences in the Platelet mRNA Landscape Portend Racial Disparities in Platelet Function and Suggest Novel Therapeutic Targets

Differences in the Platelet mRNA Landscape Portend Racial Disparities in Platelet Function and Suggest Novel Therapeutic Targets

Profiling of G-protein Coupled Receptors in Adipose Tissue and Differentiating Adipocytes Offers a Translational Resource for Obesity/Metabolic Research

Targeting PI3K/AKT signaling pathway in obesity

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