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Genetic Disruption ...
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Amrutkar, ManojGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
(author)
Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model
- Article/chapterEnglish2015
Publisher, publication year, extent ...
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2015-04-06
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American Diabetes Association,2015
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/220623
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https://gup.ub.gu.se/publication/220623URI
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https://doi.org/10.2337/db15-0060DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Understanding the molecular networks controlling ectopic lipid deposition, glucose tolerance, and insulin sensitivity is essential to identifying new pharmacological approaches to treat type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a negative regulator of glucose and insulin homeostasis based on observations in myoblasts with acute depletion of STK25 and in STK25-overexpressing transgenic mice. Here, we challenged Stk25 knockout mice and wild-type littermates with a high-fat diet and showed that STK25 deficiency suppressed development of hyperglycemia and hyperinsulinemia, improved systemic glucose tolerance, reduced hepatic gluconeogenesis, and increased insulin sensitivity. Stk25(-/-) mice were protected from diet-induced liver steatosis accompanied by decreased protein levels of acetyl-CoA carboxylase, a key regulator of both lipid oxidation and synthesis. Lipid accumulation in Stk25(-/-) skeletal muscle was reduced, and expression of enzymes controlling the muscle oxidative capacity (Cpt1, Acox1, Cs, Cycs, Ucp3) and glucose metabolism (Glut1, Glut4, Hk2) was increased. These data are consistent with our previous study of STK25 knockdown in myoblasts and reciprocal to the metabolic phenotype of Stk25 transgenic mice, reinforcing the validity of the results. The findings suggest that STK25 deficiency protects against the metabolic consequences of chronic exposure to dietary lipids and highlight the potential of STK25 antagonists for the treatment of type 2 diabetes.
Subject headings and genre
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Cansby, Emmelie,1984Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xcanem
(author)
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Chursa, UrszulaGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xchuur
(author)
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Nuñez Durán, EstherGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
(author)
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Chanclón, BelénGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
(author)
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Ståhlman, Marcus,1975Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory(Swepub:gu)xstahm
(author)
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Fridén, Vincent,1975Gothenburg University,Göteborgs universitet,Core Facilities, Centre for Physiology and Bio-Imaging,Core Facilities, Centre for Physiology and Bio-Imaging(Swepub:gu)xfrivi
(author)
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Mannerås Holm, Louise,1980Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xmanlo
(author)
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Wickman, Anna,1969Gothenburg University,Göteborgs universitet,Core Facilities, Centre for Physiology and Bio-Imaging,Core Facilities, Centre for Physiology and Bio-Imaging(Swepub:gu)xwican
(author)
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Smith, Ulf,1943Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xsmiul
(author)
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Bäckhed, Fredrik,1973Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xbafre
(author)
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Borén, Jan,1963Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory(Swepub:gu)xborej
(author)
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Howell, B. W.
(author)
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Mahlapuu, Margit,1972Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xmahma
(author)
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Göteborgs universitetInstitutionen för medicin, avdelningen för molekylär och klinisk medicin
(creator_code:org_t)
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In:Diabetes: American Diabetes Association64:8, s. 2791-28040012-17971939-327X
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Amrutkar, Manoj
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Cansby, Emmelie, ...
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Chursa, Urszula
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Chanclón, Belén
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Ståhlman, Marcus ...
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Fridén, Vincent, ...
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