Soluble CD93 Is Involved in Metabolic Dysregulation but Does Not Influence Carotid Intima-Media Thickness.

Diabetes

PubMedID: 27659228

Strawbridge RJ, Hilding A, Silveira A, Österholm C, Sennblad B, McLeod O, Tsikrika P, Foroogh F, Tremoli E, Baldassarre D, Veglia F, Rauramaa R, Smit AJ, Giral P, Kurl S, Mannarino E, Grossi E, Syvänen AC, Humphries SE, De Faire U, Östenson CG, Maegdefessel L, Hamsten A, Bäcklund A, IMPROVE Study Group. Soluble CD93 Is Involved in Metabolic Dysregulation but Does Not Influence Carotid Intima-Media Thickness. Diabetes. 2016;65(10):2888-99.
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.