Molecular and cellular biochemistry, 2018-08, Vol.445 (1-2), p.157-168
2018
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- Autor(en) / Beteiligte
- Titel
- Calcineurin is an important factor involved in glucose uptake in human adipocytes
- Ist Teil von
- Molecular and cellular biochemistry, 2018-08, Vol.445 (1-2), p.157-168
- Ort / Verlag
- New York: Springer US
- Erscheinungsjahr
- 2018
- Quelle
- SpringerLink
- Beschreibungen/Notizen
- Calcineurin inhibitors are used in immunosuppressive therapy applied after transplantation, but they are associated with major metabolic side effects including the development of new onset diabetes. Previously, we have shown that the calcineurin inhibiting drugs tacrolimus and cyclosporin A reduce adipocyte and myocyte glucose uptakes by reducing the amount of glucose transporter type 4 (GLUT4) at the cell surface, due to an increased internalization rate. However, this happens without alteration in total protein and phosphorylation levels of key proteins involved in insulin signalling or in the total amount of GLUT4. The present study evaluates possible pathways involved in the altered internalization of GLUT4 and consequent reduction of glucose uptake provoked by calcineurin inhibitors in human subcutaneous adipose tissue. Short- and long-term treatments with tacrolimus, cyclosporin A or another CNI deltamethrin (herbicide) decreased basal and insulin-dependent glucose uptake in adipocytes, without any additive effects observed when added together. However, no tacrolimus effects were observed on glucose uptake when gene transcription and protein translation were inhibited. Investigation of genes potentially involved in GLUT4 trafficking showed only a small effect on ARHGEF11 gene expression ( p < 0.05). In conlusion, the specific inhibition of calcineurin, but not that of protein phosphatases, decreases glucose uptake in human subcutaneous adipocytes, suggesting that calcineurin is an important regulator of glucose transport. This inhibitory effect is mediated via gene transcription or protein translation; however, expression of genes potentially involved in GLUT4 trafficking and endocytosis appears not to be involved in these effects.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0300-8177, 1573-4919eISSN: 1573-4919DOI: 10.1007/s11010-017-3261-0Titel-ID: cdi_swepub_primary_oai_DiVA_org_uu_360178
- Format
- –
- Schlagworte
- Adipocytes, Adipocytes - drug effects, Adipocytes - metabolism, Adipose tissue, Adult, Aged, Biochemistry, Biomedical and Life Sciences, Calcineurin, Calcineurin - metabolism, Calcineurin inhibitors, Calcineurin Inhibitors - pharmacology, Cardiology, Cell Membrane - metabolism, Cell surface, Cyclosporin A, Cyclosporine - pharmacology, Cyclosporins, Deltamethrin, Development and progression, Diabetes, Diabetes mellitus, Diabetes mellitus (insulin dependent), Diabetes therapy, Endocytosis, Female, Gene expression, Gene Expression Profiling, Genes, Glucose, Glucose - metabolism, Glucose transport, Glucose transporter, Glucose Transporter Type 4 - metabolism, Glucose uptake, Humans, Immunosuppressive agents, Immunotherapy, Inhibitors, Insulin, Insulin - metabolism, Internalization, Life Sciences, Male, Medical Biochemistry, Middle Aged, Nitriles - pharmacology, Oncology, Phosphatases, Phosphoprotein Phosphatases - antagonists & inhibitors, Phosphorylation, Protein Biosynthesis - drug effects, Proteins, Pyrethrins - pharmacology, Side effects, Signal Transduction, Signaling, Subcutaneous Fat - cytology, Tacrolimus, Tacrolimus - pharmacology, Transcription, Transcription (Genetics), Transcription, Genetic - drug effects, Translation, Translation (Genetics), Transplantation, Type 2 diabetes