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- Fonseca, Ana Catarina R. G.Uppsala universitet,Institutionen för medicinska vetenskaper,Univ Coimbra, Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal (author)
Calcineurin is an important factor involved in glucose uptake in human adipocytes
- Article/chapterEnglish2018
Publisher, publication year, extent ...
- 2018-01-27
- SPRINGER,2018
- electronicrdacarrier
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- LIBRIS-ID:oai:DiVA.org:uu-360178
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-360178URI
- https://doi.org/10.1007/s11010-017-3261-0DOI
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- Language:English
- Summary in:English
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- 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.
Subject headings and genre
- NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
- NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
- Diabetes
- Calcineurin inhibitors
- Adipose tissue
- Adipocytes
- Glucose uptake
- Gene expression
Added entries (persons, corporate bodies, meetings, titles ...)
- Carvalho, EugeniaArkansas Childrens Res Inst, Little Rock, AR 72202 USA;Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72202 USA;Univ Coimbra, Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal;Portuguese Diabet Assoc APDP, P-1250203 Lisbon, Portugal (author)
- Eriksson, JanUppsala universitet,Klinisk diabetologi och metabolism(Swepub:uu)janer909 (author)
- Pereira, Maria J,1981-Uppsala universitet,Klinisk diabetologi och metabolism(Swepub:uu)marpe927 (author)
- Uppsala universitetInstitutionen för medicinska vetenskaper (creator_code:org_t)
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- In:Molecular and Cellular Biochemistry: SPRINGER445:1-2, s. 157-1680300-81771573-4919
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