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  • 1
    Online Resource
    Online Resource
    RICORS2040: the need for collaborative research in chronic kidney disease
    Oxford University Press (OUP) ; 2022
    In:  Clinical Kidney Journal Vol. 15, No. 3 ( 2022-02-22), p. 372-387
    Details
    In: Clinical Kidney Journal, Oxford University Press (OUP), Vol. 15, No. 3 ( 2022-02-22), p. 372-387
    Abstract: Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is ‘solved’ by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020–2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true.
    Type of Medium: Online Resource
    ISSN: 2048-8505 , 2048-8513
    URL: Article
    DOI: 10.1093/ckj/sfab170
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 2
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    P0020THE NEPHRO-PROTECTIVE ROUTE OF CGMP DOES NOT COMPENSATE NPRHOGENIC DIABETES INSIPIDUS, BOTH CONDITIONS MEDIATED BY RENAL INTEGRIN LINKED KINASE (ILK)
    Oxford University Press (OUP) ; 2020
    In:  Nephrology Dialysis Transplantation Vol. 35, No. Supplement_3 ( 2020-06-01)
    Details
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: Renal ILK transgenic deletion on mice (cKD-ILK) address basal polyuria compatible with nephrogenic diabetes insipidus (NDI), due to disrupted tubular water channel aquaporin 2 (AQP2) AQP2 expression and vesicular trafficking to the apical membrane [Cano-Peñalver JL et al. FASEB J. 2014; Mamuya FA et al. Am J Physiol Renal Physiol. 2016]. An early symptom of chronic renal diseases (CKD) is NDI. ILK depletion also have a nephron-protective effect in renal damage in mice due to the increase in cGMP [Cano-Peñalver JL et al. Mol Med. 2016; de Frutos S et al. Biochim Biophys Acta Mol Basis Dis. 2019] , the latter an alternative anti-NDI mediator. Here we demonstrate that ILK-mediated regulation of AQP2, under basal or CKD contexts, does not depend on cGMP. Method cKD-ILK and controls (WT) were treated orally with a NO donor, as precursor of cGMP formation (IDN, 300mg / Kg / day) for 24 hours. Urine volume was determined as a measure of tubular functionality. Fresh kidneys from non-treated mice were cultured ex vivo with precursors of cGMP (NO donor SNP, 1 µM or cGMP analogue 8Br-cGMP, 0.2 mM) for 30 minutes. AQP2 in the apical membrane of the tubules was quantified by immunohistochemistry. More cKD-ILK and WT were subjected for 6 weeks to a diet supplemented with 0.2% adenine (A) as CKD inducer or baseline standard diet. Urine volume and total ranal AQP2 levels were determined. Results Compared to WT, cGMP axis activation in vivo did not compensate the basal NDI present in cKD-ILK and the activation ex vivo did not improve the apical presence of AQP2 in cKD-ILK. Both WT and cKD-ILK subjected to CKD showed exacerbated polyuria and decreased levels of renal AQP2, but no differences were observed between groups. Conclusion ILK regulates AQP2, both in a basal and pathological context (CKD) independent of cGMP which otherwise is nephron-protective. Our results probably explain the co-existence of cGMP increase together with AQP2 decrease observed in the cKD-ILK kidneys.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    URL: Article
    DOI: 10.1093/ndt/gfaa142.P0020
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 3
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    P0992PHARMACOLOGICAL UPREGULATION OF INTEGRIN-LINKED KINASE (ILK) REDUCES VISCERAL ADIPOSITY IN A METABOLIC SYNDROME MICE MODEL
    Oxford University Press (OUP) ; 2020
    In:  Nephrology Dialysis Transplantation Vol. 35, No. Supplement_3 ( 2020-06-01)
    Details
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: Important mechanism associated to the development of Insulin resistance (IR) are dysregulation of lipid adjustment and excessive deposition of extracellular matrix (ECM) in the visceral white adipose tissue (WAT). The transgenic depletion of the ECM-to-cell scaffold intracellular protein Integrin-linked kinase (ILK) modulates IR in WAT [Hatem-Vaquero et al. J Endocrinol. 2017] and body weight gain and adipose malfunction correlates with early downregulation of ILK expression in WAT during a short-term high fat diet (HFD) mice model [Hatem-Vaquero et al. Cell Physiol Biochem 2020] . Thus, we demonstrated that transcriptional regulation of ILK might govern the expansion of adipocytes. Between several transcriptional factors implicated in lipid metabolism, the activation of the transcription factor peroxisome proliferator activated receptor (PPAR) family member PPARβ/δ ameliorates IR. Taking in consideration that it modulates the expression of ILK in other contexts aside metabolism [Di-Poï N et al. J Steroid Biochem Mol Biol. 2003, Zhu B et al. Oncogene. 2014], here we activated PPARβ/δ in vivo and in vitro to upregulate adipose ILK expression and prevent WAT expansion. Method Adult mice were fed with either standard (STD) or HFD diets during 4 weeks and divided into groups treated with PPARβ/δ activator L-165041 (i.p. 2 mg/kg b.w per day) or vehicle for 2 additional weeks with maintained diet challenges [Lim HJ et al. Eur J Pharmacol. 2009]. Body and epidydimal WAT depot (eWAT) weights changes were compared and ILK expression was determined by RT-qPCR. Comparative studies were performed in cultured C3H10t1/2-based adipocytes where ILK expression was deliberately downregulated by the transfection of siRNAs against ILK or in control adipocytes (scramble siRNAs). After cells were treated with L-165041 (1 microM, 24h), we determined the intracellular triglyceride content (by adipo-red dye), the expression of ILK and its downstream substrate AKT (total and active p-AKT in ser473) by RT-qPCR or Western blot. Results HFD increased progressively eWAT and whole body weight gains, which coincide with increase in IR. PPARβ/δ-activated mice under STD or HFD have preventive reduction of weight gains and increased expression of ILK in eWAT. Downregulated ILK expression in culture adipocytes coincide with increased triglyceride content, whereas the activation of PPARβ/δ reduced it at the same time that increased ILK expression and activity. Conclusion We suggest ILK modulation as a novel therapeutic strategy during the obesity establishment. The pharmacological activation of PPARβ/δ increases ILK expression and activity, which correlates with a weight loss in IR-based models in vivo. Although the increased presence of ILK induces the phosphorylation of AKT, in turn one of the main mediators during insulin signalling, we cannot conclude the role of ILK-mediated AKT modulation during the reduction of the adipocyte expansion observed
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    URL: Article
    DOI: 10.1093/ndt/gfaa142.P0992
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 4
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    Indoxyl sulfate- and P-cresol-induced monocyte adhesion and migration is mediated by integrin-linked kinase-dependent podosome formation
    Springer Science and Business Media LLC ; 2022
    In:  Experimental & Molecular Medicine Vol. 54, No. 3 ( 2022-03-04), p. 226-238
    Details
    In: Experimental & Molecular Medicine, Springer Science and Business Media LLC, Vol. 54, No. 3 ( 2022-03-04), p. 226-238
    Abstract: Cardiovascular disease is an important cause of death in patients with chronic kidney disease (CKD). Protein-bound uremic toxins, such as p -cresyl and indoxyl sulfate (IS), are poorly removed during hemodialysis, leading to vascular endothelial dysfunction and leukocyte extravasation. These processes can be related to dynamic adhesion structures called podosomes. Several studies have indicated the role of integrin-linked kinase (ILK) in the accumulation of integrin-associated proteins in podosomes. Here, we investigated the involvement of ILK and podosome formation in the adhesion and extravasation of monocytes under p -cresol (pc) and IS exposure. Incubation of THP-1 human monocyte cells with these toxins upregulated ILK kinase activity. Together, both toxins increased cell adhesion, podosome formation, extracellular matrix degradation, and migration of THP-1 cells, whereas ILK depletion with specific small interfering RNAs suppressed these processes. Interestingly, F-actin colocalized with cortactin in podosome cores, while ILK was colocalized in podosome rings under toxin stimulation. Podosome Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP) and AKT protein depletion demonstrated that monocyte adhesion depends on podosome formation and that the ILK/AKT signaling pathway is involved in these processes. Ex vivo experiments showed that both toxins induced adhesion and podosome formation in leukocytes from wild-type mice, whereas these effects were not observed in leukocytes of conditional ILK-knockdown animals. In summary, under pc and IS stimulation, monocytes increase podosome formation and transmigratory capacity through an ILK/AKT signaling pathway-dependent mechanism, which could lead to vascular injury. Therefore, ILK could be a potential therapeutic target for the treatment of vascular damage associated with CKD.
    Type of Medium: Online Resource
    ISSN: 2092-6413
    URL: Article
    DOI: 10.1038/s12276-022-00738-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 5
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    Efecto protector de la deleción de la quinasa ligada a integrinas (ILK) en la fibrosis y el daño vascular asociado a la enfermedad renal crónica
    Universidad de Alcala ; 2019
    In:  Dianas Vol. 8, No. 1 ( 2019-3-31)
    Details
    In: Dianas, Universidad de Alcala, Vol. 8, No. 1 ( 2019-3-31)
    Type of Medium: Online Resource
    ISSN: 1886-8746
    URL: Issue
    URL: Journal
    URL: Article
    DOI: 10.37536/DIANAS.2019.8.1
    DOI: 10.37536/DIANAS
    DOI: 10.37536/DIANAS.2019.8.1.24
    Language: Spanish
    Publisher: Universidad de Alcala
    Publication Date: 2019
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  • 6
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    P0675LEUCOCYTE PODOSOME FORMATION AND ADHESION TO ENDOTHELIUM IS MEDIATED BY INTEGRIN LINKED KINASE IN CHRONIC KIDNEY DISEASE (CKD)
    Oxford University Press (OUP) ; 2020
    In:  Nephrology Dialysis Transplantation Vol. 35, No. Supplement_3 ( 2020-06-01)
    Details
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: Patients with CKD have a higher risk of developing cardiovascular diseases. Protein-bound uremic toxins, such as p-cresol (pc) and indoxyl-sulfate (IS), are retention solutes, poorly removed during hemodialysis. They lead to endothelial dysfunction inducing the expression of adhesion molecules and leucocyte adhesion to endothelium. Monocyte extravasation can be carried out by dynamic adhesion structures called podosomes. Integrin-linked kinase (ILK), a kinase and an intracellular scaffold protein, links the cell-adhesion receptors, integrins and growth factors to the actin cytoskeleton and to a range of signalling pathways. We demonstrate the role of ILK in the accumulation of integrin-associated proteins inside the podosomes. The aim of this study was to investigate if ILK is involved in uremic toxin-induced leucocyte podosome formation and adhesion under uremic conditions that simulate CKD. Method In vitro experiments were carried out in human cell line of leukemic monocytes, THP-1. We tested the effect of uremic toxins on cell viability and ILK expression levels or activation by performing dose and time-response experiments. Cells were exposed to IS (25-100 µg ml-1) plus pc (10-100 µg ml-1) both combined, for different times. ILK expression levels were determined by Western Blot and RT-qPCR and its kinase activity was tested by its downstream effector GSK-3β phosphorylated levels. Cell adhesion of THP-1 cells stained with cell tracker to a monolayer of human endothelial cells (EA.hy926) and podosome formation and cell adhesion of THP-1 cells stained with phalloidin to a fibronectin extracellular matrix, was determined by fluorescence confocal microscopy. ILK co-localization with podosome specific protein cortactin was assessed by fluorescence confocal microscopy. For ex vivo experiments in ILK conditional-knockdown mice (cKD-ILK), male CRE-LOX mice were injected with tamoxifen (cKD-ILK) or vehicle (wild-type, WT), to induce ILK deletion. Peripheral blood mononuclear cells (PBMCs) were obtained and treated with uremic toxins. Cell adhesion to a fibronectin extracellular matrix was determined by cell count of the percentage of attached cells against the total cells collected. Results Our data suggests that uremic toxins did not induce toxicity in THP-1 cells. Furthermore, ILK was activated by uremic toxins both at low and high concentrations, without changes in the protein expression. In the cell adhesion assay to the endothelium, uremic toxins induces an increase of THP-1 cells adhesion, which is completely abolished when ILK is knocked down by ILK siRNA, both at low and high toxins concentrations. Similar results were obtained from the cell adhesion assay to the fibronectin extracellular matrix. Moreover, uremic toxins induced podosome formation in THP-1 cells, even at low concentrations, compared to the control, while ILK knockdown abrogated almost completely fibronectin adhesion and podosome formation in uremic toxin-treated cells. Interestingly, we tested that ILK co-localize with cortactin in podosomes, which confirmed the implication of ILK in podosome structures formation induced by uremic toxins. In cKD-ILK PBMC mice the transgenic ILK depletion significantly decrease non-excised ILK mRNA levels. These cKD-ILK PBMC mice exhibited a lower adhesion to the fibronectin extracellular matrix compared to WT. By last, uremic toxins induced a significant increase of mice PBMCs adhesion in WT animals compared to the control that was significantly lower in PBMCs of cKD-ILK animals. Conclusion These data suggest that ILK plays a critical role in the required processes for leukocyte extravasation. ILK deletion may prevent podosome formation and adhesion of leucocytes, decreasing the endothelial and vascular damage caused by the accumulation of uremic toxins in CKD. Therefore, ILK could be a potential therapeutic target for the treatment of vascular damage associated with CKD.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    URL: Article
    DOI: 10.1093/ndt/gfaa142.P0675
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 7
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    P0672CALPAINS 1 AND 2 ARE INCREASED DURING THE DEVELOPMENT OF CHRONIC KIDNEY DAMAGE IN MICE FED WITH AN ADENINE RICH DIET
    Oxford University Press (OUP) ; 2020
    In:  Nephrology Dialysis Transplantation Vol. 35, No. Supplement_3 ( 2020-06-01)
    Details
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: Calpains are intracellular cysteine proteases that play a critical role in cell remodeling, being involved in multiple biological processes linked to tissue damage and repair mechanisms. In addition, they are released into the circulation, being able to carry out systemic actions with pathological consequences. The aim of this study was to investigate the role of calpains in the progression of chronic kidney disease (CKD) in an experimental model of chronic renal damage induced by adenine. Method We induced an experimental model of CKD, in mice fed for 2 weeks with an adenine-supplemented diet (0.2% adenine) (A). Animals receiving this diet develop a tubulointerstitial damage resembling that is observed in human CKD. Mice with standard diet were used as controls (C). Renal function was assessed by measuring serum blood urea nitrogen (BUN) and creatinine (mg/dl). Fibrosis markers (collagen type I and fibronectin) were determined by RT-qPCR. Changes in the renal content of calpains 1 and 2 were analyzed by western blot (protein content), and RT-qPCR (mRNA expression). Results Our results show functional and structural changes at renal level in the adenine-fed mice, with increased BUN (A: 72 mg/dl, C: 28 mg/dl, p & lt; 0.05), creatinine (A: 0.58 mg/dl, C: 0.25 mg/dl, p & lt; 0.05), collagen type I mRNA expression (A: 12.9 units, C: 1.2 units, p & lt; 0.05) and fibronectin mRNA expression (A: 3.46 units, C: 1.3 units, p & lt; 0.05). Furthermore, protein content of calpains 1 (A: 1.27 units, C: 0.78 units, p & lt; 0.05) and 2 (A: 1.30 units, C: 0.66 units, p & lt; 0.05) was significantly higher in adenine-fed mice when compared to control. At the same time, we observed a significant increase in gene expression of both calpain 1 (A: 4.21 units, C: 0.51 units, p & lt; 0.05) and 2 (A: 4.93 units, C: 0.56 units, p & lt; 0.05) in the adenine model regarding to mice with standard diet. Our results demonstrate that calpain 1 and 2 expression in renal tissue increases as CKD progresses. Interestingly, we found statistically significant correlations between renal calpains 1 and 2 protein and mRNA content and plasma BUN and creatinine (p & lt; 0.05, r between 0.79 and 0.92), as well as protein expression of calpain 2 and mRNA expression of collagen type I (p & lt; 0.05, r = 0.76). These data suggest a potential direct relationship between renal calpain 1 and 2 content and loss of renal function, in part due probably to the modulation of the fibrotic changes, in adenine fed mice. Conclusion We suggest an implication of calpains 1 and 2 in the development of CKD. Thus, effective calpain blockade or downregulation could be useful as a therapeutic strategy to prevent CKD. Further experiments will be necessary to establish the relationship between these factors.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    URL: Article
    DOI: 10.1093/ndt/gfaa142.P0672
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 8
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    Incremento de calpaínas 1 y 2 durante el desarrollo de enfermedad renal crónica en ratones alimentados con una dieta rica en adenina
    Universidad de Alcala ; 2020
    In:  Dianas Vol. 9, No. 1 ( 2020-3-31)
    Details
    In: Dianas, Universidad de Alcala, Vol. 9, No. 1 ( 2020-3-31)
    Type of Medium: Online Resource
    ISSN: 1886-8746
    URL: Issue
    URL: Journal
    URL: Article
    DOI: 10.37536/DIANAS.2020.9.1
    DOI: 10.37536/DIANAS
    DOI: 10.37536/DIANAS.2020.9.1.73
    Language: Spanish
    Publisher: Universidad de Alcala
    Publication Date: 2020
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  • 9
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    La formación de podosomas y la adhesión de leucocitos es mediada por la Quinasa Ligada a Integrinas en la enfermedad renal crónica (ERC)
    Universidad de Alcala ; 2020
    In:  Dianas Vol. 9, No. 1 ( 2020-3-31)
    Details
    In: Dianas, Universidad de Alcala, Vol. 9, No. 1 ( 2020-3-31)
    Type of Medium: Online Resource
    ISSN: 1886-8746
    URL: Issue
    URL: Journal
    URL: Article
    DOI: 10.37536/DIANAS.2020.9.1
    DOI: 10.37536/DIANAS
    DOI: 10.37536/DIANAS.2020.9.1.74
    Language: Spanish
    Publisher: Universidad de Alcala
    Publication Date: 2020
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  • 10
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    P0980IMPLICATIONS OF ADIPOSE EARLY DOWNREGULATION OF INTEGRIN-LINKED KINASE (ILK) IN THE DEVELOPMENT OF METABOLIC SYNDROME IN MICE
    Oxford University Press (OUP) ; 2020
    In:  Nephrology Dialysis Transplantation Vol. 35, No. Supplement_3 ( 2020-06-01)
    Details
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: Insulin resistance (IR)-related metabolic disorders, such as diabetes type 2 and obesity, are linked to renal and cardiovascular risk. Unfortunately, they lack a better prognosis before their full establishment. An important mechanism associated to the IR development is the dysregulation of lipolysis in white adipose tissue (WAT), which is driven by the excessive lipid accumulation, together with inflammation and the excessive deposition of ECM components such as collagens and fibronectin, known as fibrosis. The intracellular lipid adjustment is affected by changes in the expression and activity of the hormone-sensitive lipase (HSL) and the intracellular and circulating balance of the lipolysis products glycerol and free fatty acids. We published that transgenic depletion of the scaffold intracellular protein Integrin-linked kinase (ILK), one of the adhesome translators of the ECM signals, modulates IR in WAT [Hatem-Vaquero et al. J Endocrinol. 2017]. We also published that ILK downregulation in WAT is an early event in a short-term high fat diet (HFD) mice model that correlates with a faster insulin sensitivity loss, accompanied with an early increase of body weight and the erratic expression of WAT adipokines and metabolites transporters. [Hatem-Vaquero et al. Cell Physiol Biochem 2020] . Here we used in vivo and in vitro approaches to decode the role of ILK downregulation during WAT expansion and altered lipolysis. Method Adult mice with global transgenic downregulation of ILK expression (cKD-ILK) and littermates without that depletion (CT) were fed with either standard (STD) or high fat (HFD) diets during 2 and 6 weeks. We determined the weight changes on body and WAT depots, epidydimal (eWAT) and subcutaneous (scWAT), and the circulating lypolisis product glycerol. The expression of ECM component fibronectin (FN), fibrosis marker TGF-beta and the glycerol transporter AQP3 were determined in eWAT by RT-qPCR or Western blot. Comparative studies were performed in cultured C3H10t1/2-based adipocytes where ILK expression was deliberately downregulated by the transfection of siRNAs against ILK or in control adipocytes (scramble siRNAs). We determined the expression of ILK, total and active HSL isoforms (HSL, p-HSL s660) by RT-qPCR or Western blot and the intracellular fat droplet content (by adipo-red dye) Results HFD increased progressively CT eWAT, scWAT and whole body weight gains. HFD-fed cKD-ILK have an earlier increase of body and eWAT weights. However, the scWAT weight ratio against eWAT was inverted in the same cKD-ILK animals. This early depot-specific response to HFD coincide with increase in IR [Wajchenberg BL. Endocr Rev 2000]. HFD-fed cKD-ILK WAT early expressed altered levels of fibrotic markers (TGF-beta and Fibronectin). HFD-fed cKD-ILK shown a temporary increase of circulating glycerol and its WAT transporter AQP3. In cultured adipocytes with downregulated expression of ILK, the intracellular fat droplet was increased and the HSL contain and its lipolysis activity (measured as levels of p-HSL isoform) were reduced. Conclusion We suggest ILK as a modulator during the obesity establishment. Considering the observed relation between ILK expression with the altered lipolysis and fibrosis patterns observed in visceral WAT, ILK downregulation may be a predictive value and probably its pharmacological upregulation may be a novel therapeutic strategy against obesity and IR.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    URL: Article
    DOI: 10.1093/ndt/gfaa142.P0980
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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