title: Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes.
abstract: Chronic inflammation plays a key role in both type 1 and type 2 diabetes. Cytokine and chemokine production within the islets in a diabetic milieu results in β-cell failure and diabetes progression. Identification of targets, which both prevent macrophage activation and infiltration into islets and restore β-cell functionality is essential for effective diabetes therapy. We report that certain Sialic-acid-binding immunoglobulin-like-lectins (siglecs) are expressed in human pancreatic islets in a cell-type specific manner. Siglec-7 was expressed on β-cells and down-regulated in type 1 and type 2 diabetes and in infiltrating activated immune cells. Over-expression of Siglec-7 in diabetic islets reduced cytokines, prevented β-cell dysfunction and apoptosis and reduced recruiting of migrating monocytes. Our data suggest that restoration of human Siglec-7 expression may be a novel therapeutic strategy targeted to both inhibition of immune activation and preservation of β-cell function and survival.
authors.affiliation: Centre for Biomolecular Interactions Bremen, University of Bremen, Germany.|Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Cancer Genomics Netherlands, Utrecht, The Netherlands.
authors.forename: Gitanjali
authors.initials: G
authors.lastname: Dharmadhikari
authors.affiliation: Centre for Biomolecular Interactions Bremen, University of Bremen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Stolz
authors.affiliation: Centre for Biomolecular Interactions Bremen, University of Bremen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hauke
authors.affiliation: Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, RILD Building, Barrack Road, Exeter EX2 5DW, UK.
authors.forename: Noel G
authors.initials: NG
authors.lastname: Morgan
authors.affiliation: Glycobiology Research and Training Center and Departments of Medicine and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
authors.affiliation: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Cancer Genomics Netherlands, Utrecht, The Netherlands.|Leiden University Medical Center, Department of Medicine, Section of Nephrology and Section of Endocrinology, Leiden, the Netherlands.
authors.forename: Eelco
authors.initials: E
authors.lastname: de Koning
authors.affiliation: Centre for Biomolecular Interactions Bremen, University of Bremen, Germany.
authors.forename: Sørge
authors.initials: S
authors.lastname: Kelm
authors.affiliation: Centre for Biomolecular Interactions Bremen, University of Bremen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Maedler
mesh_terms: D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D009928:Organ Specificity
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D016207:Cytokines; D037102:Lectins; C402206:SIGLEC7 protein, human