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

Rona J. Strawbridge, Agneta Hilding, Angela Silveira, Cecilia Österholm, Bengt Sennblad, Olga McLeod, Panagiota Tsikrika, Fariba Foroogh, Elena Tremoli, Damiano Baldassarre, Fabrizio Veglia, Rainer Rauramaa, Andries J. Smit, Phillipe Giral, Sudhir Kurl, Elmo Mannarino, Enzo Grossi, Ann Christine Syvänen, Steve E. Humphries, Ulf De FaireClaes Göran Östenson, Lars Maegdefessel, Anders Hamsten, Alexandra Bäcklund

Research output: Contribution to journalArticle

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 apoe2/2 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.

Original languageEnglish
Pages (from-to)2888-2899
Number of pages12
JournalDiabetes
Volume65
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    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., ... Bäcklund, A. (2016). Soluble CD93 is involved in metabolic dysregulation but does not influence carotid intima-media thickness. Diabetes, 65(10), 2888-2899. https://doi.org/10.2337/db15-1333