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Direct activation o...
Direct activation of glucose transport in primary human myotubes after activation of peroxisome proliferator-activated receptor delta
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- Krämer, David Kitz (author)
- Department of Surgical Science, Karolinska Institute, Stockholm, Sweden; Dept. of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
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- Al-Khalili, Lubna (author)
- Karolinska Institutet
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- Perrini, Sebastio (author)
- Department of Surgical Science, Karolinska Institute, Stockholm, Sweden; Dept. of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
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- Skogsberg, Josefin (author)
- Karolinska Institutet
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- Wretenberg, Per, 1963- (author)
- Karolinska Institutet
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- Kannisto, Katja (author)
- Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden
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- Wallberg-Henriksson, Harriet (author)
- Karolinska Institutet
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- Ehrenborg, Ewa (author)
- Karolinska Institutet
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- Zierath, Juleen R. (author)
- Karolinska Institutet
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- Krook, Anna (author)
- Karolinska Institutet
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Karolinska Institutet Department of Surgical Science, Karolinska Institute, Stockholm, Sweden; Dept of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden (creator_code:org_t)
- Alexandria, USA : American Diabetes Association, 2005
- 2005
- English.
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In: Diabetes. - Alexandria, USA : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:4, s. 1157-1163
- Related links:
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https://doi.org/10.2...
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http://diabetes.diab...
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https://urn.kb.se/re...
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Abstract
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- Activators of peroxisome proliferator-activated receptor (PPAR)gamma have been studied intensively for their insulin-sensitizing properties and antidiabetic effects. Recently, a specific PPARdelta activator (GW501516) was reported to attenuate plasma glucose and insulin levels when administered to genetically obese ob/ob mice. This study was performed to determine whether specific activation of PPARdelta has direct effects on insulin action in skeletal muscle. Specific activation of PPARdelta using two pharmacological agonists (GW501516 and GW0742) increased glucose uptake independently of insulin in differentiated C2C12 myotubes. In cultured primary human skeletal myotubes, GW501516 increased glucose uptake independently of insulin and enhanced subsequent insulin stimulation. PPARdelta agonists increased the respective phosphorylation and expression of AMP-activated protein kinase 1.9-fold (P < 0.05) and 1.8-fold (P < 0.05), of extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (MAPK) 2.2-fold (P < 0.05) and 1.7-fold (P < 0.05), and of p38 MAPK 1.2-fold (P < 0.05) and 1.4-fold (P < 0.05). Basal and insulin-stimulated protein kinase B/Akt was unaltered in cells preexposed to PPARdelta agonists. Preincubation of myotubes with the p38 MAPK inhibitor SB203580 reduced insulin- and PPARdelta-mediated increase in glucose uptake, whereas the mitogen-activated protein kinase kinase inhibitor PD98059 was without effect. PPARdelta agonists reduced mRNA expression of PPARdelta, sterol regulatory element binding protein (SREBP)-1a, and SREBP-1c (P < 0.05). In contrast, mRNA expression of PPARgamma, PPARgamma coactivator 1, GLUT1, and GLUT4 was unaltered. Our results provide evidence to suggest that PPARdelta agonists increase glucose metabolism and promote gene regulatory responses in cultured human skeletal muscle. Moreover, we provide biological validation of PPARdelta as a potential target for antidiabetic therapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- art (subject category)
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Diabetes
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- By the author/editor
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Krämer, David Ki ...
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Al-Khalili, Lubn ...
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Perrini, Sebasti ...
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Skogsberg, Josef ...
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Wretenberg, Per, ...
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Kannisto, Katja
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Wallberg-Henriks ...
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Ehrenborg, Ewa
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Zierath, Juleen ...
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Krook, Anna
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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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Örebro University
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Karolinska Institutet