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; Cansby, Emmelie; Chursa, Urszula; Nuñez-Durán, Esther; Chanclón, Belén; Ståhlman, Marcus; Fridén, Vincent; Mannerås-Holm, Louise; Wickman, Anna; Smith, Ulf; Bäckhed, Gert Fredrik; Borén, Jan; Howell, Brian W; Mahlapuu, Margit.

In: Diabetes, Vol. 64, No. 8, 08.2015, p. 2791-804.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Amrutkar, M, Cansby, E, Chursa, U, Nuñez-Durán, E, Chanclón, B, Ståhlman, M, Fridén, V, Mannerås-Holm, L, Wickman, A, Smith, U, Bäckhed, GF, Borén, J, Howell, BW & Mahlapuu, M 2015, 'Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model', Diabetes, vol. 64, no. 8, pp. 2791-804. https://doi.org/10.2337/db15-0060

APA

Amrutkar, M., Cansby, E., Chursa, U., Nuñez-Durán, E., Chanclón, B., Ståhlman, M., ... Mahlapuu, M. (2015). Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model. Diabetes, 64(8), 2791-804. https://doi.org/10.2337/db15-0060

Vancouver

Amrutkar M, Cansby E, Chursa U, Nuñez-Durán E, Chanclón B, Ståhlman M et al. Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model. Diabetes. 2015 Aug;64(8):2791-804. https://doi.org/10.2337/db15-0060

Author

Amrutkar, Manoj ; Cansby, Emmelie ; Chursa, Urszula ; Nuñez-Durán, Esther ; Chanclón, Belén ; Ståhlman, Marcus ; Fridén, Vincent ; Mannerås-Holm, Louise ; Wickman, Anna ; Smith, Ulf ; Bäckhed, Gert Fredrik ; Borén, Jan ; Howell, Brian W ; Mahlapuu, Margit. / Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model. In: Diabetes. 2015 ; Vol. 64, No. 8. pp. 2791-804.

Bibtex

@article{ef80ce1f6403417f98dde1c580432ee8,
title = "Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model",
abstract = "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.",
keywords = "Acetyl-CoA Carboxylase, Animals, Blood Glucose, Body Composition, Body Weight, Diabetes Mellitus, Type 2, Diet, High-Fat, Fatty Liver, Gluconeogenesis, Glucose Tolerance Test, Hyperglycemia, Hyperinsulinism, Insulin, Insulin Resistance, Intracellular Signaling Peptides and Proteins, Lipid Metabolism, Liver, Male, Mice, Mice, Knockout, Protein-Serine-Threonine Kinases",
author = "Manoj Amrutkar and Emmelie Cansby and Urszula Chursa and Esther Nu{\~n}ez-Dur{\'a}n and Bel{\'e}n Chancl{\'o}n and Marcus St{\aa}hlman and Vincent Frid{\'e}n and Louise Manner{\aa}s-Holm and Anna Wickman and Ulf Smith and B{\"a}ckhed, {Gert Fredrik} and Jan Bor{\'e}n and Howell, {Brian W} and Margit Mahlapuu",
note = "{\circledC} 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.",
year = "2015",
month = "8",
doi = "10.2337/db15-0060",
language = "English",
volume = "64",
pages = "2791--804",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "8",

}

RIS

TY - JOUR

T1 - Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model

AU - Amrutkar, Manoj

AU - Cansby, Emmelie

AU - Chursa, Urszula

AU - Nuñez-Durán, Esther

AU - Chanclón, Belén

AU - Ståhlman, Marcus

AU - Fridén, Vincent

AU - Mannerås-Holm, Louise

AU - Wickman, Anna

AU - Smith, Ulf

AU - Bäckhed, Gert Fredrik

AU - Borén, Jan

AU - Howell, Brian W

AU - Mahlapuu, Margit

N1 - © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

PY - 2015/8

Y1 - 2015/8

N2 - 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.

AB - 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.

KW - Acetyl-CoA Carboxylase

KW - Animals

KW - Blood Glucose

KW - Body Composition

KW - Body Weight

KW - Diabetes Mellitus, Type 2

KW - Diet, High-Fat

KW - Fatty Liver

KW - Gluconeogenesis

KW - Glucose Tolerance Test

KW - Hyperglycemia

KW - Hyperinsulinism

KW - Insulin

KW - Insulin Resistance

KW - Intracellular Signaling Peptides and Proteins

KW - Lipid Metabolism

KW - Liver

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Protein-Serine-Threonine Kinases

U2 - 10.2337/db15-0060

DO - 10.2337/db15-0060

M3 - Journal article

VL - 64

SP - 2791

EP - 2804

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 8

ER -

ID: 156087818