A Nerstedt1, E Cansby, C X Andersson, M Laakso, A Stančáková, M Blüher, U Smith, M Mahlapuu. 1. The Lundberg Laboratory for Diabetes Research, Center of Excellence for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine/Diabetes, The Sahlgrenska Academy, University of Gothenburg, Blå stråket 5, 413 45 Göteborg, Sweden.
Abstract
AIMS/HYPOTHESIS: This study investigates the role of serine/threonine protein kinase 25 (STK25), a member of the sterile 20 (STE20) superfamily of kinases, in the regulation of skeletal muscle metabolism. METHODS: The effect of depleting STK25 in muscle cells was studied by reducing the mRNA and protein content of this target in the rat myoblast cell line L6 by small interfering (si)RNA. The changes in the mRNA and protein levels of several members of the fatty acid oxidative and glucose metabolic pathways were measured by quantitative real-time (qRT)-PCR and western blot. The rate of palmitate oxidation and glucose uptake was measured after transfection with siRNA for Stk25. Expression of STK25 was also evaluated in skeletal muscle biopsies from 41 white Europid men and women with normal and impaired glucose tolerance and type 2 diabetes using qRT-PCR. RESULTS: We demonstrate that partial depletion of STK25 increases the expression of uncoupling protein 3 (Ucp3), accompanied by increased lipid oxidation, in myoblasts. In addition, a reduced level of STK25 enhances the expression of Slc2a1 (also known as Glut1), Slc2a4 (also known as Glut4) and hexokinase 2, and correspondingly, improves insulin-stimulated glucose uptake in muscle cells. Consistent with these results, significantly higher STK25 levels were observed in the skeletal muscle of type 2 diabetic patients, compared with individuals with normal glucose tolerance. CONCLUSIONS/ INTERPRETATION: This is the first study indicating a possible role for STK25 in the regulation of glucose and lipid metabolism in L6 myoblasts. This kinase appears to be an interesting new mediator to be evaluated for therapeutic intervention in type 2 diabetes and related complications, as controlled increase in lipid oxidation and insulin-stimulated glucose uptake in skeletal muscle is favourable and can restore energy balance in metabolically compromised states.
AIMS/HYPOTHESIS: This study investigates the role of serine/threonine protein kinase 25 (STK25), a member of the sterile 20 (STE20) superfamily of kinases, in the regulation of skeletal muscle metabolism. METHODS: The effect of depleting STK25 in muscle cells was studied by reducing the mRNA and protein content of this target in the rat myoblast cell line L6 by small interfering (si)RNA. The changes in the mRNA and protein levels of several members of the fatty acid oxidative and glucose metabolic pathways were measured by quantitative real-time (qRT)-PCR and western blot. The rate of palmitate oxidation and glucose uptake was measured after transfection with siRNA for Stk25. Expression of STK25 was also evaluated in skeletal muscle biopsies from 41 white Europid men and women with normal and impaired glucose tolerance and type 2 diabetes using qRT-PCR. RESULTS: We demonstrate that partial depletion of STK25 increases the expression of uncoupling protein 3 (Ucp3), accompanied by increased lipid oxidation, in myoblasts. In addition, a reduced level of STK25 enhances the expression of Slc2a1 (also known as Glut1), Slc2a4 (also known as Glut4) and hexokinase 2, and correspondingly, improves insulin-stimulated glucose uptake in muscle cells. Consistent with these results, significantly higher STK25 levels were observed in the skeletal muscle of type 2 diabeticpatients, compared with individuals with normal glucose tolerance. CONCLUSIONS/ INTERPRETATION: This is the first study indicating a possible role for STK25 in the regulation of glucose and lipid metabolism in L6 myoblasts. This kinase appears to be an interesting new mediator to be evaluated for therapeutic intervention in type 2 diabetes and related complications, as controlled increase in lipid oxidation and insulin-stimulated glucose uptake in skeletal muscle is favourable and can restore energy balance in metabolically compromised states.
Authors: Emilio Nogueira; Miguel Fidalgo; Arpad Molnar; John Kyriakis; Thomas Force; Juan Zalvide; Celia M Pombo Journal: J Biol Chem Date: 2008-03-25 Impact factor: 5.157
Authors: José P Silva; Irina G Shabalina; Eric Dufour; Natasa Petrovic; Emma C Backlund; Kjell Hultenby; Rolf Wibom; Jan Nedergaard; Barbara Cannon; Nils-Göran Larsson Journal: EMBO J Date: 2005-11-10 Impact factor: 11.598
Authors: Michal Pravenec; Laura M Saba; Václav Zídek; Vladimír Landa; Petr Mlejnek; Jan Šilhavý; Miroslava Šimáková; Hynek Strnad; Jaroslava Trnovská; Vojtěch Škop; Martina Hüttl; Irena Marková; Olena Oliyarnyk; Hana Malínská; Ludmila Kazdová; Harry Smith; Boris Tabakoff Journal: Physiol Genomics Date: 2017-11-10 Impact factor: 3.107
Authors: Manoj Amrutkar; Emmelie Cansby; Urszula Chursa; Esther Nuñez-Durán; Belén Chanclón; Marcus Ståhlman; Vincent Fridén; Louise Mannerås-Holm; Anna Wickman; Ulf Smith; Fredrik Bäckhed; Jan Borén; Brian W Howell; Margit Mahlapuu Journal: Diabetes Date: 2015-04-06 Impact factor: 9.461