Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model

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Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model

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

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

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

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

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

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

Fridén, Vincent, 1975 (author): Gothenburg University,Göteborgs universitet,Core Facilities, Centre for Physiology and Bio-Imaging,Core Facilities, Centre for Physiology and Bio-Imaging

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

Wickman, Anna, 1969 (author): Gothenburg University,Göteborgs universitet,Core Facilities, Centre for Physiology and Bio-Imaging,Core Facilities, Centre for Physiology and Bio-Imaging

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

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

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

Howell, B. W. (author)

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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2015-04-06
2015
English.
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:8, s. 2791-2804

Related links:: https://diabetes.dia...; show more...; https://gup.ub.gu.se...; https://doi.org/10.2...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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

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By the author/editor: Amrutkar, Manoj; Cansby, Emmelie, ...; Chursa, Urszula; Nuñez Durán, Est ...; Chanclón, Belén; Ståhlman, Marcus ...; show more...; Fridén, Vincent, ...; Mannerås Holm, L ...; Wickman, Anna, 1 ...; Smith, Ulf, 1943; Bäckhed, Fredrik ...; Borén, Jan, 1963; Howell, B. W.; Mahlapuu, Margit ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

Articles in the publication: Diabetes

By the university: University of Gothenburg

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