title: Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes.
abstract: Reduced insulin release has been linked to defect exocytosis in β-cells. However, whether expression of genes suggested to be involved in the exocytotic process (exocytotic genes) is altered in pancreatic islets from patients with type 2 diabetes (T2D), and correlate to insulin secretion, needs to be further investigated. Analysing expression levels of 23 exocytotic genes using microarray revealed reduced expression of five genes in human T2D islets (χ(2)=13.25; p<0.001). Gene expression of STX1A, SYT4, SYT7, SYT11, SYT13, SNAP25 and STXBP1 correlated negatively to in vivo measurements of HbA1c levels and positively to glucose stimulated insulin secretion (GSIS) in vitro in human islets. STX1A, SYT4 and SYT11 protein levels correspondingly decreased in human T2D islets. Moreover, silencing of SYT4 and SYT13 reduced GSIS in INS1-832/13 cells. Our data support that reduced expression of exocytotic genes contributes to impaired insulin secretion, and suggest decreased expression of these genes as part of T2D pathogenesis.
authors.affiliation: Islet Cell Exocytosis, Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Andersson
authors.forename: Anders H
authors.initials: AH
authors.lastname: Olsson
authors.forename: Jonathan L S
authors.initials: JL
authors.lastname: Esguerra
authors.forename: Emilia
authors.initials: E
authors.lastname: Heimann
authors.forename: Claes
authors.initials: C
authors.lastname: Ladenvall
authors.forename: Anna
authors.initials: A
authors.lastname: Edlund
authors.forename: Albert
authors.initials: A
authors.lastname: Salehi
authors.forename: Jalal
authors.initials: J
authors.lastname: Taneera
authors.forename: Eva
authors.initials: E
authors.lastname: Degerman
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
authors.forename: Lena
authors.initials: L
authors.lastname: Eliasson
mesh_terms: D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005089:Exocytosis / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D020868:Gene Silencing; D055106:Genome-Wide Association Study; D005947:Glucose / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D046509:Tissue Culture Techniques
chemical_list: D005947:Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D012333:RNA, Messenger; D034741:RNA, Small Interfering