Soluble CD93 Is Involved in Metabolic Dysregulation but Does Not Influence Carotid Intima-Media Thickness
2016 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 10, 2888-2899 p.Article in journal (Refereed) Published
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 6 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.
Place, publisher, year, edition, pages
2016. Vol. 65, no 10, 2888-2899 p.
Endocrinology and Diabetes
IdentifiersURN: urn:nbn:se:uu:diva-311222DOI: 10.2337/db15-1333ISI: 000388372900010PubMedID: 27659228OAI: oai:DiVA.org:uu-311222DiVA: diva2:1059611
FunderSwedish Heart Lung Foundation, 20120615, 20130664, 20140186Swedish Research Council, 8691, 0593Knut and Alice Wallenberg FoundationSwedish Foundation for Strategic Research Stockholm County CouncilEU, FP7, Seventh Framework Programme, IMI/115006Swedish Diabetes AssociationForte, Swedish Research Council for Health, Working Life and WelfareNovo NordiskMagnus Bergvall FoundationStiftelsen Gamla Tjänarinnor