Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/36264270http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36264270http://www.w3.org/2000/01/rdf-schema#comment"

Background

Tetraspanin-7 (Tspan7) is an islet autoantigen involved in autoimmune type 1 diabetes and known to regulate β-cell L-type Ca2+ channel activity. However, the role of Tspan7 in pancreatic β-cell function is not yet fully understood.

Methods

Histological analyses were conducted using immunostaining. Whole-body metabolism was tested using glucose tolerance test. Islet hormone secretion was quantified using static batch incubation or dynamic perifusion. β-cell transmembrane currents, electrical activity and exocytosis were measured using whole-cell patch-clamping and capacitance measurements. Gene expression was studied using mRNA-sequencing and quantitative PCR.

Results

Tspan7 is expressed in insulin-containing granules of pancreatic β-cells and glucagon-producing α-cells. Tspan7 knockout mice (Tspan7y/- mouse) exhibit reduced body weight and ad libitum plasma glucose but normal glucose tolerance. Tspan7y/- islets have normal insulin content and glucose- or tolbutamide-stimulated insulin secretion. Depolarisation-triggered Ca2+ current was enhanced in Tspan7y/- β-cells, but β-cell electrical activity and depolarisation-evoked exocytosis were unchanged suggesting that exocytosis was less sensitive to Ca2+ . TSPAN7 knockdown (KD) in human pseudo-islets led to a significant reduction in insulin secretion stimulated by 20 mM K+ . Transcriptomic analyses show that TSPAN7 KD in human pseudo-islets correlated with changes in genes involved in hormone secretion, apoptosis and ER stress. Consistent with rodent β-cells, exocytotic Ca2+ sensitivity was reduced in a human β-cell line (EndoC-βH1) following Tspan7 KD.

Conclusion

Tspan7 is involved in the regulation of Ca2+ -dependent exocytosis in β-cells. Its function is more significant in human β-cells than their rodent counterparts."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.org/dc/terms/identifier"doi:10.1111/dme.14984"xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"Clark A."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"Zhang Q."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"Singh S.P."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"Nawaz S."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"MacDonald P.E."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"Manning Fox J.E."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"Spigelman A.F."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"Hastoy B."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"McLaughlin K."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"Knudsen J.G."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"Denwood G."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"Acreman S."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/author"Cutteridge J."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/name"Diabet Med"xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/pages"e14984"xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/title"Loss of tetraspanin-7 expression reduces pancreatic beta-cell exocytosis Capisup>2+pi/sup> sensitivity but has limited effect on systemic metabolism."xsd:string
http://purl.uniprot.org/citations/36264270http://purl.uniprot.org/core/volume"39"xsd:string
http://purl.uniprot.org/citations/36264270http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36264270
http://purl.uniprot.org/citations/36264270http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/36264270
http://purl.uniprot.org/uniprot/#_B4DDG0-mappedCitation-36264270http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36264270
http://purl.uniprot.org/uniprot/#_B4DEA5-mappedCitation-36264270http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36264270
▶