TY - JOUR
T1 - Soluble CD93 is involved in metabolic dysregulation but does not influence carotid intima-media thickness
AU - Strawbridge, Rona J.
AU - Hilding, Agneta
AU - Silveira, Angela
AU - Österholm, Cecilia
AU - Sennblad, Bengt
AU - McLeod, Olga
AU - Tsikrika, Panagiota
AU - Foroogh, Fariba
AU - Tremoli, Elena
AU - Baldassarre, Damiano
AU - Veglia, Fabrizio
AU - Rauramaa, Rainer
AU - Smit, Andries J.
AU - Giral, Phillipe
AU - Kurl, Sudhir
AU - Mannarino, Elmo
AU - Grossi, Enzo
AU - Syvänen, Ann Christine
AU - Humphries, Steve E.
AU - De Faire, Ulf
AU - Östenson, Claes Göran
AU - Maegdefessel, Lars
AU - Hamsten, Anders
AU - Bäcklund, Alexandra
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
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U2 - 10.2337/db15-1333
DO - 10.2337/db15-1333
M3 - Article
AN - SCOPUS:84989187926
VL - 65
SP - 2888
EP - 2899
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 10
ER -