Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Protein kinase STK25 aggr… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Protein kinase STK25 aggravates the severity of non-alcoholic fatty pancreas disease in mice

Artikel i vetenskaplig tidskrift
Författare Esther Nuñez Durán
Belén Chanclón
Silva Sütt
Joana Real
Hanns-Ulrich Marschall
Ingrid Wernstedt Asterholm
Emmelie Cansby
Margit Mahlapuu
Publicerad i Journal of Endocrinology
Volym 234
Nummer/häfte 1
Sidor 15-27
ISSN 0022-0795
Publiceringsår 2017
Publicerad vid Wallenberglaboratoriet
Institutionen för neurovetenskap och fysiologi
Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi
Institutionen för medicin, avdelningen för molekylär och klinisk medicin
Sidor 15-27
Språk en
Länkar doi.org/10.1530/joe-17-0018
Ämnesord non-alcoholic fatty pancreas disease, ectopic lipid storage, beta-cell dysfunction, endoplasmic-reticulum stress, beta-cell apoptosis, insulin-resistance, metabolic syndrome, skeletal-muscle, tca cycle, dysfunction, liver, steatosis, defects, Endocrinology & Metabolism
Ämneskategorier Klinisk medicin, Kemi

Sammanfattning

Characterising the molecular networks that negatively regulate pancreatic beta-cell function is essential for understanding the underlying pathogenesis and developing new treatment strategies for type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator of ectopic fat storage, meta-inflammation, and fibrosis in liver and skeletal muscle. Here, we assessed the role of STK25 in control of progression of non-alcoholic fatty pancreas disease in the context of chronic exposure to dietary lipids in mice. We found that overexpression of STK25 in high-fat-fed transgenic mice aggravated diet-induced lipid storage in the pancreas compared with that of wild-type controls, which was accompanied by exacerbated pancreatic inflammatory cell infiltration, stellate cell activation, fibrosis and apoptosis. Pancreas of Stk25 transgenic mice also displayed a marked decrease in islet beta/alpha-cell ratio and alteration in the islet architecture with an increased presence of a-cells within the islet core, whereas islet size remained similar between genotypes. After a continued challenge with a high-fat diet, lower levels of fasting plasma insulin and C-peptide, and higher levels of plasma leptin, were detected in Stk25 transgenic vs wild-type mice. Furthermore, the glucose-stimulated insulin secretion was impaired in high-fat-fed Stk25 transgenic mice during glucose tolerance test, in spite of higher net change in blood glucose concentrations compared with wild-type controls, suggesting islet beta-cell dysfunction. In summary, this study unravels a role for STK25 in determining the susceptibility to diet-induced nonalcoholic fatty pancreas disease in mice in connection to obesity. Our findings highlight STK25 as a potential drug target for metabolic disease.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?