Soluble CD93 Is Involved in Metabolic Dysregulation but Does Not Influence Carotid Intima-Media Thickness
Articolo
Data di Pubblicazione:
2016
Citazione:
Soluble CD93 Is Involved in Metabolic Dysregulation but Does Not Influence Carotid Intima-Media Thickness / R.J. Strawbridge, A. Hilding, A. Silveira, C. Österholm, B. Sennblad, O. Mcleod, P. Tsikrika, F. Foroogh, E. Tremoli, D. Baldassarre, F. Veglia, R. Rauramaa, A.J. Smit, P. Giral, S. Kurl, E. Mannarino, E. Grossi, A. Syvänen, S.E. Humphries, U. de Faire, C. Östenson, L. Maegdefessel, A. Hamsten, A. Bäcklund. - In: DIABETES. - ISSN 0012-1797. - 65:10(2016 Oct), pp. 2888-2899. [10.2337/db15-1333]
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.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
R.J. Strawbridge, A. Hilding, A. Silveira, C. Österholm, B. Sennblad, O. Mcleod, P. Tsikrika, F. Foroogh, E. Tremoli, D. Baldassarre, F. Veglia, R. Rauramaa, A.J. Smit, P. Giral, S. Kurl, E. Mannarino, E. Grossi, A. Syvänen, S.E. Humphries, U. de Faire, C. Östenson, L. Maegdefessel, A. Hamsten, A. Bäcklund
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