uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Fatty acid-induced oxidation and triglyceride formation is higher in insulin-producing MIN6 cells exposed to oleate compared to palmitate
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. (Peter Bergsten)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2010 (English)In: Journal of Cellular Biochemistry, ISSN 0730-2312, E-ISSN 1097-4644, Vol. 111, no 2, 497-507 p.Article in journal (Refereed) Published
Abstract [en]

Palmitate negatively affects insulin secretion and apoptosis in the pancreatic β-cell. The detrimental effects are abolished by elongating and desaturating the fatty acid into oleate. To investigate mechanisms of how the two fatty acids differently affect β-cell function and apoptosis, lipid handling was determined in MIN6 cells cultured in the presence of the fatty acids palmitate (16:0) and oleate (18:1) and also corresponding monounsaturated fatty acid palmitoleate (16:1) and saturated fatty acid stearate (18:0). Insulin secretion was impaired and apoptosis accentuated in palmitate-, and to some extent, stearate-treated cells. Small or no changes in secretion or apoptosis were observed in cells exposed to palmitoleate or oleate. Expressions of genes associated with fatty acid esterification (SCD1, DGAT1, DGAT2 and FAS) were augmented in cells exposed to palmitate or stearate but only partially (DGAT2) in palmitoleate- or oleate-treated cells. Nevertheless, levels of triglycerides were highest in cells exposed to oleate. Similarly, fatty acid oxidation was most pronounced in oleate-treated cells despite comparable up-regulation of CPT1 after treatment of cells with the four different fatty acids. The difference in apoptosis between palmitate and stearate was paralleled by similar differences in levels of markers of endoplasmic reticulum (ER) stress in cells exposed to the two fatty acids. Palmitate-induced ER stress was not accounted for by ceramide de novo synthesis. In conclusion, although palmitate initiated stronger expression changes consistent with lipid accumulation and combustion in MIN6 cells, rise in triglyceride levels and fatty acid oxidation was favored specifically in cells exposed to oleate.

Place, publisher, year, edition, pages
2010. Vol. 111, no 2, 497-507 p.
Keyword [en]
Ceramide, apoptosis, endoplasmic reticulum stress, triglyceride, lipotoxicity, palmitate, oleate
National Category
Cell and Molecular Biology
Research subject
Medical Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-129570DOI: 10.1002/jcb.22734ISI: 000282482400026PubMedID: 20524206OAI: oai:DiVA.org:uu-129570DiVA: diva2:344340
Available from: 2010-08-18 Created: 2010-08-18 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Palmitate-induced Apoptosis in Insulin-producing β-cells
Open this publication in new window or tab >>Palmitate-induced Apoptosis in Insulin-producing β-cells
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Type 2 diabetes is a disease characterized by the inability of pancreatic β-cells to secrete sufficient amounts of insulin to maintain normoglycemia. Increased levels of saturated fatty acids such as palmitate are believed to contribute to β-cell failure and the development of the disease. In the present thesis, mechanisms behind palmitate-induced β-cell apoptosis were explored.

Palmitate augmented insulin secretion after short exposure to the fatty acid, but attenuated the secretory response after longer exposure. Elevated levels of palmitate increased endoplasmic reticulum (ER) stress and induced apoptosis. When insulin secretion was inhibited by diazoxide, palmitate-induced ER stress and apoptosis were reduced. In comparison to palmitate, the mono-unsaturated fatty acid oleate increased neither ER stress nor apoptosis. Furthermore, shuttling of fatty acids into triglycerides and β-oxidation was favored in cells exposed to oleate compared to palmitate. When the levels of stearoyl-CoA desaturase 1 (SCD1), the enzyme responsible for conversion of saturated to mono-unsaturated fatty acids, were reduced, up-regulation of ER chaperones and components of the proteasome was observed. Cells with reduced levels of SCD1 showed increased sensitivity to palmitate, as exposure to the fatty acid increased levels of ER stress and apoptosis. Palmitate-induced apoptosis of the β-cell has been linked to alterations in sphingolipid metabolism. In cells with reduced levels of sphingosine kinase (SphK) 2, palmitate failed to induce apoptosis, and ER stress was reduced. Furthermore, SphK2 was required for the palmitate-induced activation of c-Jun N-terminal kinase (JNK). In contrast, knockdown of SphK1 sensitized the cell to palmitate-induced apoptosis independently of ER stress.

In summary, palmitate induces β-cell apoptosis, which is partly dependent on the induction of ER stress. The mechanisms investigated support the notion that increased protein load on the ER, low degree of triglyceride formation and β-oxidation, and perturbations in sphingolipid metabolism contribute to palmitate-induced apoptosis in insulin-producing β-cells.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 55 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 589
Keyword
ER stress, apoptosis, palmitate, sphingosine-1-phosphate, ceramide, beta-cell, fatty acid
National Category
Cell and Molecular Biology
Research subject
Medical Cell Biology
Identifiers
urn:nbn:se:uu:diva-129575 (URN)978-91-554-7869-8 (ISBN)
Public defence
2010-10-01, B41, BMC, Husargatan 3, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2010-09-09 Created: 2010-08-19 Last updated: 2011-07-07Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedhttp://onlinelibrary.wiley.com/doi/10.1002/jcb.22734/abstract

Authority records BETA

Thörn, Kristofer

Search in DiVA

By author/editor
Thörn, Kristofer
By organisation
Department of Medical Cell Biology
In the same journal
Journal of Cellular Biochemistry
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 375 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf