Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes.

Summary, in English

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.

• Författare: Sofia A Andersson; Anders H Olsson; Jonathan L S Esguerra; Emilia Heimann; Claes Ladenvall; Anna Edlund; S Albert Salehi; Jalal Taneera; Eva Degerman; Leif Groop; Charlotte Ling; Lena Eliasson
• Avdelning/ar: Diabetes - epigenetik; Translationell Muskel Forskning; Signaltransduktionsforskning; Institutionen för kliniska vetenskaper, Malmö; Diabetes - öcellsexocytos; Islet cell physiology; EXODIAB: Excellence of Diabetes Research in Sweden
• Publiceringsår: 2012
• Språk: Engelska
• Sidor: 36-45
• Publikation/Tidskrift/Serie: Molecular and Cellular Endocrinology
• Volym: 364
• Issue: 1-2
• Fulltext: - 491 kB; Download statistics
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/22939844?dopt=Abstract; http://dx.doi.org/10.1016/j.mce.2012.08.009
• Dokumenttyp: Artikel i tidskrift
• Förlag: Elsevier
• Ämne: Endocrinology and Diabetes
• Status: Published
• Forskningsgrupp: Diabetes - Epigenetics; Genomics, Diabetes and Endocrinology; Insulin Signal Transduction; Diabetes - Islet Cell Exocytosis; Islet cell physiology
• ISBN/ISSN/Övrigt: ISSN: 1872-8057