Soluble CD93 is involved in metabolic dysregulation but does not influence carotid intima-media thickness

Strawbridge, R. J. et al. (2016) Soluble CD93 is involved in metabolic dysregulation but does not influence carotid intima-media thickness. Diabetes, 65(10), pp. 2888-2899. (doi:10.2337/db15-1333) (PMID:27659228)

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Abstract

Type 2 diabetes and cardiovascular disease are complex disorders involving metabolic and inflammatory mechanisms. Here we investigated whether sCD93, a group XIV c-type lectin of the endosialin family, plays a role in metabolic dysregulation or carotid intima-media thickness (IMT). Although no association was observed between sCD93 and IMT, sCD93 levels were significantly lower in subjects with type 2 diabetes (n = 901, mean ± SD 156.6 ± 40.0 ng/mL) compared with subjects without diabetes (n = 2,470, 164.1 ± 44.8 ng/mL, P < 0.0001). Genetic variants associated with diabetes risk (DIAGRAM Consortium) did not influence sCD93 levels (individually or combined in a single nucleotide polymorphism score). In a prospective cohort, lower sCD93 levels preceded the development of diabetes. Consistent with this, a cd93-deficient mouse model (in addition to apoe deficiency) demonstrated no difference in atherosclerotic lesion development compared with apoe−/− cd93-sufficient littermates. However, cd93-deficient mice showed impaired glucose clearance and insulin sensitivity (compared with littermate controls) after eating a high-fat diet. The expression of cd93 was observed in pancreatic islets, and leaky vessels were apparent in cd93-deficient pancreases. We further demonstrated that stress-induced release of sCD93 is impaired by hyperglycemia. Therefore, we propose CD93 as an important component in glucometabolic regulation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Strawbridge, Dr Rona
Authors: Strawbridge, R. J., Hilding, A., Silveira, A., Österholm, C., Sennblad, B., McLeod, O., Tsikrika, P., Foroogh, F., Tremoli, E., Baldassarre, D., Veglia, F., Rauramaa, R., Smit, A. J., Giral, P., Kurl, S., Mannarino, E., Grossi, E., Syvänen, A.-C., Humphries, S. E., de Faire, U., Östenson, C.-G., Maegdefessel, L., Hamsten, A., and Bäcklund, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
Journal Name:Diabetes
Publisher:American Diabetes Association
ISSN:0012-1797
ISSN (Online):1939-327X
Published Online:22 September 2016
Copyright Holders:Copyright © 2016 American Diabetes Association
First Published:First published in Diabetes 65(10):2888-2899
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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