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The effect of type 2 diabetes on CD36 expression and the uptake of oxLDL Diabetes affects CD36 and oxLDL uptake
UCSF, CA 94158 USA; SFVAMC, CA 94121 USA; Tohoku Univ, Japan.
UCSF, CA 94158 USA; SFVAMC, CA 94121 USA; Tohoku Univ, Japan.
Linköping University. UCSF, CA 94158 USA; SFVAMC, CA 94121 USA.
UCSF, CA 94158 USA; SFVAMC, CA 94121 USA; Tohoku Univ, Japan.
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2020 (English)In: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 334, article id 113461Article in journal (Refereed) Published
Abstract [en]

We investigated whether type 2 diabetes mellitus (T2DM), a risk factor of stroke, affects the level of scavenger receptor CD36 and the uptake of its ligand, oxidized LDL (oxLDL); and whether pioglitazone, a drug that enhances CD36, promotes oxLDL uptake. Compared to normoglycemic db/+ mice, adult db/db mice showed a pronounced reduction in surface CD36 expression on myeloid cells from the blood, brain, and bone marrow as detected by flow cytometry, which correlated with elevated plasma soluble-CD36 as determined by ELISA. Increased CD36 expression was found in brain macrophages and microglia of both genotypes 7 days after ischemic stroke. In juvenile db/db mice, prior to obesity and hyperglycemia, only a mild reduction of surface CD36 was found in blood neutrophils, while all other myeloid cells showed no difference relative to the db/+ strain. In vivo, oral pioglitazone treatment for four weeks increased CD36 levels on myeloid cells in db/db mice. In vitro, uptake of oxLDL by bone marrow derived macrophages (BMDMs) of db/db mice was reduced relative to db/+ mice in normal glucose medium. OxLDL uptake inversely correlated with glucose levels in the medium in db/+ BMDMs. Furthermore, pioglitazone restored oxLDL uptake by BMDMs from db/db mice cultured in high glucose. Our data suggest that T2DM is associated with reduced CD36 on adult myeloid cells, and pioglitazone enhances CD36 expression in db/db cells. T2DM or high glucose reduces oxLDL uptake while pioglitazone enhances oxLDL uptake. Our findings provide new insight into the mechanism by which pioglitazone may be beneficial in the treatment of insulin resistance.

Place, publisher, year, edition, pages
Academic Press, 2020. Vol. 334, article id 113461
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Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-171654DOI: 10.1016/j.expneurol.2020.113461ISI: 000587389600017PubMedID: 32926860Scopus ID: 2-s2.0-85090862348OAI: oai:DiVA.org:liu-171654DiVA, id: diva2:1505101
Note

Funding Agencies|NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 NS102886]; VA merit awardUS Department of Veterans Affairs [I01BX003335]; Research Career Scientist awardUS Department of Veterans Affairs [IK6BX004600]

Available from: 2020-11-30 Created: 2020-11-30 Last updated: 2020-12-08Bibliographically approved

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