GLP-1 improves adipose tissue glyoxalase activity and capillarization improving insulin sensitivity in type 2 diabetes

doi:10.1016/j.phrs.2020.105198

. 2020 Nov:161:105198.

doi: 10.1016/j.phrs.2020.105198. Epub 2020 Sep 14.

GLP-1 improves adipose tissue glyoxalase activity and capillarization improving insulin sensitivity in type 2 diabetes

Tiago Rodrigues¹, Patrícia Borges², Laura Mar², Daniela Marques², Miguel Albano³, Hans Eickhoff⁴, Catarina Carrêlo², Bruno Almeida⁵, Salomé Pires⁶, Margarida Abrantes⁶, Beatriz Martins⁷, Cristina Uriarte³, Filomena Botelho⁶, Pedro Gomes³, Sónia Silva⁸, Raquel Seiça¹, Paulo Matafome⁹

Affiliations

¹ Institute of Physiology and Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra (FMUC), Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
² Institute of Physiology and Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra (FMUC), Portugal.
³ Department of Surgery, Universitary Hospital Center of Coimbra, Portugal.
⁴ Institute of Physiology and Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra (FMUC), Portugal; Obesity Center, Hospital de Santiago, Setúbal, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
⁵ Association for the Protection of Portuguese Diabetic Patients (APDP), Lisbon, Portugal.
⁶ Institute of Biophysics and iCBR, FMUC, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
⁷ iCBR, FMUC, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
⁸ Obesity Center, Hospital de Santiago, Setúbal, Portugal; Faculty of Farmacy, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
⁹ Institute of Physiology and Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra (FMUC), Portugal; Instituto Politécnico de Coimbra, Coimbra Health School (ESTeSC), Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal. Electronic address: paulo.matafome@uc.pt.

PMID: 32942016
DOI: 10.1016/j.phrs.2020.105198

GLP-1 improves adipose tissue glyoxalase activity and capillarization improving insulin sensitivity in type 2 diabetes

Tiago Rodrigues et al. Pharmacol Res. 2020 Nov.

. 2020 Nov:161:105198.

doi: 10.1016/j.phrs.2020.105198. Epub 2020 Sep 14.

Authors

Affiliations

¹ Institute of Physiology and Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra (FMUC), Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
² Institute of Physiology and Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra (FMUC), Portugal.
³ Department of Surgery, Universitary Hospital Center of Coimbra, Portugal.
⁴ Institute of Physiology and Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra (FMUC), Portugal; Obesity Center, Hospital de Santiago, Setúbal, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
⁵ Association for the Protection of Portuguese Diabetic Patients (APDP), Lisbon, Portugal.
⁶ Institute of Biophysics and iCBR, FMUC, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
⁷ iCBR, FMUC, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
⁸ Obesity Center, Hospital de Santiago, Setúbal, Portugal; Faculty of Farmacy, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
⁹ Institute of Physiology and Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra (FMUC), Portugal; Instituto Politécnico de Coimbra, Coimbra Health School (ESTeSC), Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal. Electronic address: paulo.matafome@uc.pt.

PMID: 32942016
DOI: 10.1016/j.phrs.2020.105198

Abstract

Methylglyoxal was shown to impair adipose tissue capillarization and insulin sensitivity in obese models. We hypothesized that glyoxalase-1 (GLO-1) activity could be diminished in the adipose tissue of type 2 diabetic obese patients. Moreover, we assessed whether such activity could be increased by GLP-1-based therapies in order to improve adipose tissue capillarization and insulin sensitivity. GLO-1 activity was assessed in visceral adipose tissue of a cohort of obese patients. The role of GLP-1 in modulating GLO-1 was assessed in type 2 diabetic GK rats submitted to sleeve gastrectomy or Liraglutide treatment, in the adipose tissue angiogenesis assay and in the HUVEC cell line. Glyoxalase-1 activity was decreased in visceral adipose tissue of pre-diabetic and diabetic obese patients, together with other markers of adipose tissue dysfunction and correlated with increased HbA1c levels. Decreased adipose tissue GLO-1 levels in GK rats were increased by sleeve gastrectomy and Liraglutide, being associated with overexpression of angiogenic and vasoactive factors, as well as insulin receptor phosphorylation (Tyr1161). Moreover, GLP-1 increased adipose tissue capillarization and HUVEC proliferation in a glyoxalase-dependent manner. Lower adipose tissue GLO-1 activity was observed in dysmetabolic patients, being a target for GLP-1 in improving adipose tissue capillarization and insulin sensitivity.

Keywords: Adipose tissue; Capillarization; GLP-1; Glyoxalase; Insulin resistance; Liraglutide.

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GLP-1 improves adipose tissue glyoxalase activity and capillarization improving insulin sensitivity in type 2 diabetes

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GLP-1 improves adipose tissue glyoxalase activity and capillarization improving insulin sensitivity in type 2 diabetes

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