Increased expression of STK25 leads to impaired glucose utilization and insulin sensitivity in mice challenged with a high‐fat diet

• Published in: The FASEB journal 2013-09, Vol.27 (9), p.3660-3671
• Main Authors: Cansby, Emmelie, Amrutkar, Manoj, Holm, Louise Mannerås, Nerstedt, Annika, Reyahi, Azadeh, Stenfeldt, Elin, Borén, Jan, Carlsson, Peter, Smith, Ulf, Zierath, Juleen R., Mahlapuu, Margit
• Format: Article
• Language: English
• Subjects: Adipocytes - metabolism; Animals; Body Composition - genetics; Body Composition - physiology; Calorimetry, Indirect; Cell and Molecular Biology; Cell- och molekylärbiologi; Cells, Cultured; Diet, High-Fat - adverse effects; Glucose - metabolism; Glucose Tolerance Test; Immunohistochemistry; Insulin Resistance - genetics; Insulin Resistance - physiology; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Male; metabolic balance; Mice; Mice, Inbred C57BL; Mice, Transgenic; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Reverse Transcriptase Polymerase Chain Reaction; serine/threonine protein kinase 25; type 2 diabetes
• ISSN: 0892-6638; 1530-6860; 1530-6860
• DOI: 10.1096/fj.13-228494

Partial depletion of serine/threonine protein kinase 25 (STK25), a member of the Ste20 superfamily of kinases, increases lipid oxidation and glucose uptake in rodent myoblasts. Here we show that transgenic mice overexpressing STK25, when challenged with a high‐fat diet, develop reduced glucose tolerance and insulin sensitivity compared to wild‐type siblings, as evidenced by impairment in glucose and insulin tolerance tests as well as in euglycemic‐hyperin‐sulinemic clamp studies. The fasting plasma insulin concentration was elevated in Stk25 transgenic mice compared to wild‐type littermates (4.9±0.8 vs. 2.6±0.4 ng/ml after 17 wk on high‐fat diet, P