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Genetic Disruption ...
Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model
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- Amrutkar, Manoj (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Cansby, Emmelie, 1984 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Chursa, Urszula (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Nuñez Durán, Esther (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Chanclón, Belén (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Ståhlman, Marcus, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Fridén, Vincent, 1975 (author)
- Gothenburg University,Göteborgs universitet,Core Facilities, Centre for Physiology and Bio-Imaging,Core Facilities, Centre for Physiology and Bio-Imaging
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- Mannerås Holm, Louise, 1980 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Wickman, Anna, 1969 (author)
- Gothenburg University,Göteborgs universitet,Core Facilities, Centre for Physiology and Bio-Imaging,Core Facilities, Centre for Physiology and Bio-Imaging
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- Smith, Ulf, 1943 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Bäckhed, Fredrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Borén, Jan, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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Howell, B. W. (author)
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- Mahlapuu, Margit, 1972 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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(creator_code:org_t)
- 2015-04-06
- 2015
- English.
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:8, s. 2791-2804
- Related links:
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https://diabetes.dia...
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https://gup.ub.gu.se...
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https://doi.org/10.2...
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Abstract
Subject headings
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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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- HEPATIC INSULIN-RESISTANCE
- AMYLOID PRECURSOR PROTEIN
- ACETYL-COA
- CARBOXYLASE-1
- DOUBLECORTIN-LIKE-KINASE
- FATTY-ACID OXIDATION
- NEURONAL
- MIGRATION
- SKELETAL-MUSCLE
- LIPIDOMIC ANALYSIS
- CELL-DEATH
- MICE
- Endocrinology & Metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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Diabetes
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- By the author/editor
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Amrutkar, Manoj
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Cansby, Emmelie, ...
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Chursa, Urszula
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Nuñez Durán, Est ...
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Chanclón, Belén
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Ståhlman, Marcus ...
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show more...
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Fridén, Vincent, ...
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Mannerås Holm, L ...
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Wickman, Anna, 1 ...
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Smith, Ulf, 1943
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Bäckhed, Fredrik ...
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Borén, Jan, 1963
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Howell, B. W.
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Mahlapuu, Margit ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Diabetes
- By the university
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University of Gothenburg