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Addition of exogeno...
Addition of exogenous sodium palmitate increases the IAPP/insulin mRNA ratio via GPR40 in human EndoC-beta H1 cells
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- Krizhanovskii, Camilla (author)
- Karolinska Institutet,Uppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab,Sodertalje Hosp, Dept Internal Med, Sodertalje, Sweden.
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- Fred, Rikard G (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab
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- Oskarsson, Marie E. (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab
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- Westermark, Gunilla T. (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab
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- Welsh, Nils (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2017-10-05
- 2017
- English.
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In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 122:3, s. 149-159
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Abstract
Subject headings
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- Background: Enhanced IAPP production may contribute to islet amyloid formation in type 2 diabetes. The objective of this study was to determine the effects of the saturated fatty acid palmitate on IAPP levels in human beta-cells. Methods: EndoC-beta H1 cells and human islets were cultured in the presence of sodium palmitate. Effects on IAPP/insulin mRNA expression and secretion were determined using real-time qPCR/ELISA. Pharmacological activators and/or inhibitors and RNAi were used to determine the underlying mechanisms. Results: We observed that EndoC-beta H1 cells exposed to palmitate for 72 h displayed decreased expression of Pdx-1 and MafA and increased expression of thioredoxin-interacting protein (TXNIP), reduced insulin mRNA expression and glucose-induced insulin secretion, as well as increased IAPP mRNA expression and secretion. Further, these effects were independent of fatty acid oxidation, but abolished in response to GPR40 inhibition/downregulation. In human islets both a high glucose concentration and palmitate promoted increased IAPP mRNA levels, resulting in an augmented IAPP/insulin mRNA ratio. This was paralleled by elevated IAPP/insulin protein secretion and content ratios. Conclusions: Addition of exogenous palmitate to human beta-cells increased the IAPP/insulin expression ratio, an effect contributed to by activation of GPR40. These findings may be pertinent to our understanding of the islet amyloid formation process.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Amyloid
- fatty acids
- insulin
- islet amyloid polypeptide (IAPP)
- palmitate
Publication and Content Type
- ref (subject category)
- art (subject category)
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