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Interleukin-22 reve...
Interleukin-22 reverses human islet dysfunction and apoptosis triggered by hyperglycemia and LIGHT
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- Abadpour, Shadab (författare)
- Oslo University Hospital, Oslo, Norway
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- Halvorsen, Bente (författare)
- Oslo University Hospital, Oslo, Norway
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- Sahraoui, Afaf (författare)
- University of Oslo, Oslo, Norway
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- Korsgren, Olle (författare)
- Uppsala universitet,Klinisk immunologi
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- Aukrust, Pål (författare)
- Oslo University Hospital, Oslo, Norway
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- Scholz, Hanne (författare)
- Oslo University Hospital, Oslo, Norway
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(creator_code:org_t)
- 2018
- 2018
- Engelska.
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Ingår i: Journal of Molecular Endocrinology. - 0952-5041 .- 1479-6813. ; 60:3, s. 171-183
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Interleukin (IL)-22 has recently been suggested as an anti-inflammatory cytokine that could protect the islet cells from inflammation- and glucose-induced toxicity. We have previously shown that the tumor necrosis factor family member, LIGHT can impair human islet function at least partly via pro-apoptotic effects. Herein, we aimed to investigate the protective role of IL-22 on human islets exposed to the combination of hyperglycemia and LIGHT. First, we found up-regulation of LIGHT receptors (LTβR and HVEM) in engrafted human islets exposed to hyperglycemia (>11 mM) for 17 days post transplantation by using a double islet transplantation mouse model as well as in human islets cultured with high glucose (HG) (20mM glucose) + LIGHT in vitro and this latter effect was attenuated by IL-22. The effect of HG + LIGHT impairing glucose stimulated insulin secretion was reversed by IL-22. The harmful effect of HG + LIGHT on human islet function seemed to involve enhanced endoplasmic reticulum stress evidenced by up-regulation of p-IRE1α and BiP, elevated secretion of pro-inflammatory cytokines (IL-6, IL-8, IP-10 and MCP-1) and the pro-coagulant mediator tissue factor (TF) release and apoptosis in human islets, whereas all these effects were at least partly reversed by IL-22. Our findings suggest that IL-22 could counteract the harmful effects of LIGHT/hyperglycemia on human islet cells and potentially support the strong protective effect of IL-22 on impaired islet function and survival.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- art (ämneskategori)
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