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

    1. Margit Mahlapuu1
    1. 1Department of Molecular and Clinical Medicine, Lundberg Laboratory for Diabetes Research, Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
    2. 2Department of Metabolic Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
    3. 3Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
    1. Correspondence should be addressed to M Mahlapuu; Email: Margit.Mahlapuu{at}


    Characterising the molecular networks that negatively regulate pancreatic β-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 β/α-cell ratio and alteration in the islet architecture with an increased presence of α-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 β-cell dysfunction. In summary, this study unravels a role for STK25 in determining the susceptibility to diet-induced non-alcoholic fatty pancreas disease in mice in connection to obesity. Our findings highlight STK25 as a potential drug target for metabolic disease.

    • Received 18 April 2017
    • Accepted 25 April 2017
    • Made available online as an Accepted Preprint 25 April 2017
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    1. J Endocrinol 234 15-27
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