Increased expression of STK25 leads to impaired glucose utilization and insulin sensitivity in mice challenged with a high‐fat diet

Partial depletion of serine/threonine protein kinase 25 (STK25), a member of the Ste20 superfamily of kinases, increases lipid oxidation and glucose uptake in rodent myoblasts. Here we show that transgenic mice overexpressing STK25, when challenged with a high‐fat diet, develop reduced glucose toler...

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Published in:The FASEB journal 2013-09, Vol.27 (9), p.3660-3671
Main Authors: Cansby, Emmelie, Amrutkar, Manoj, Holm, Louise Mannerås, Nerstedt, Annika, Reyahi, Azadeh, Stenfeldt, Elin, Borén, Jan, Carlsson, Peter, Smith, Ulf, Zierath, Juleen R., Mahlapuu, Margit
Format: Article
Language:English
Subjects:
Adipocytes - metabolism
Animals
Body Composition - genetics
Body Composition - physiology
Calorimetry, Indirect
Cell and Molecular Biology
Cell- och molekylärbiologi
Cells, Cultured
Diet, High-Fat - adverse effects
Glucose - metabolism
Glucose Tolerance Test
Immunohistochemistry
Insulin Resistance - genetics
Insulin Resistance - physiology
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
Male
metabolic balance
Mice
Mice, Inbred C57BL
Mice, Transgenic
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Reverse Transcriptase Polymerase Chain Reaction
serine/threonine protein kinase 25
type 2 diabetes
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container_title The FASEB journal
container_volume 27
creator Cansby, Emmelie
Amrutkar, Manoj
Holm, Louise Mannerås
Nerstedt, Annika
Reyahi, Azadeh
Stenfeldt, Elin
Borén, Jan
Carlsson, Peter
Smith, Ulf
Zierath, Juleen R.
Mahlapuu, Margit
description Partial depletion of serine/threonine protein kinase 25 (STK25), a member of the Ste20 superfamily of kinases, increases lipid oxidation and glucose uptake in rodent myoblasts. Here we show that transgenic mice overexpressing STK25, when challenged with a high‐fat diet, develop reduced glucose tolerance and insulin sensitivity compared to wild‐type siblings, as evidenced by impairment in glucose and insulin tolerance tests as well as in euglycemic‐hyperin‐sulinemic clamp studies. The fasting plasma insulin concentration was elevated in Stk25 transgenic mice compared to wild‐type littermates (4.9±0.8 vs. 2.6±0.4 ng/ml after 17 wk on high‐fat diet, P
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Hepatic triglycerides and glycogen were elevated (1.6‐ and 1.4‐fold, respectively; P&lt;0.05) and expression of key enzymes regulating lipogenesis (Fasn), glycogen synthesis (Gck), and gluconeogenesis (G6pc, Fbp1) was increased in the liver of the transgenic mice. Our findings suggest that overexpression of STK25 in conditions of excess dietary fuels associates with a shift in the metabolic balance in peripheral tissues from lipid oxidation to storage, leading to a systemic insulin resistance.—Cansby, E., Amrutkar, M., Mannerås Holm, L., Nerstedt, A., Reyahi, A., Stenfeldt, E., Borén, J., Carlsson, P., Smith, U., Zierath, J.R., Mahlapuu, M. Increased expression of STK25 leads to impaired glucose utilization and insulin sensitivity in mice challenged with a high‐fat diet. 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subjects Adipocytes - metabolism
Animals
Body Composition - genetics
Body Composition - physiology
Calorimetry, Indirect
Cell and Molecular Biology
Cell- och molekylärbiologi
Cells, Cultured
Diet, High-Fat - adverse effects
Glucose - metabolism
Glucose Tolerance Test
Immunohistochemistry
Insulin Resistance - genetics
Insulin Resistance - physiology
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
Male
metabolic balance
Mice
Mice, Inbred C57BL
Mice, Transgenic
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Reverse Transcriptase Polymerase Chain Reaction
serine/threonine protein kinase 25
type 2 diabetes
title Increased expression of STK25 leads to impaired glucose utilization and insulin sensitivity in mice challenged with a high‐fat diet
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