In vivo metabolic effects after acute activation of skeletal muscle Gs signaling
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In vivo metabolic effects after acute activation of skeletal muscle Gs signaling. / Meister, Jaroslawna; Bone, Derek B J; Knudsen, Jonas Roland; Barella, Luiz F; Liu, Liu; Lee, Regina; Gavrilova, Oksana; Chen, Min; Weinstein, Lee S; Kleinert, Maximilian; Jensen, Thomas Elbenhardt; Wess, Jürgen.
I: Molecular Metabolism, Bind 55, 101415, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - In vivo metabolic effects after acute activation of skeletal muscle Gs signaling
AU - Meister, Jaroslawna
AU - Bone, Derek B J
AU - Knudsen, Jonas Roland
AU - Barella, Luiz F
AU - Liu, Liu
AU - Lee, Regina
AU - Gavrilova, Oksana
AU - Chen, Min
AU - Weinstein, Lee S
AU - Kleinert, Maximilian
AU - Jensen, Thomas Elbenhardt
AU - Wess, Jürgen
N1 - Copyright © 2021. Published by Elsevier GmbH.
PY - 2022
Y1 - 2022
N2 - Objective: The goal of this study was to determine the glucometabolic effects of acute activation of Gs signaling in skeletal muscle (SKM) in vivo and its contribution to whole-body glucose homeostasis.Methods: To address this question, we studied mice that express a Gs-coupled designer G protein-coupled receptor (Gs-DREADD or GsD) selectively in skeletal muscle. We also identified two Gs-coupled GPCRs that are endogenously expressed by SKM at relatively high levels (β2-adrenergic receptor and CRF2 receptor) and studied the acute metabolic effects of activating these receptors in vivo by highly selective agonists (clenbuterol and urocortin 2 (UCN2), respectively).Results: Acute stimulation of GsD signaling in SKM impaired glucose tolerance in lean and obese mice by decreasing glucose uptake selectively into SKM. However, the acute metabolic effects following agonist activation of β2-adrenergic and, potentially, CRF2 receptors appear primarily mediated by altered insulin release. Clenbuterol injection improved glucose tolerance by increasing insulin secretion in lean mice. In SKM, clenbuterol stimulated glycogen breakdown. UCN2 injection resulted in decreased glucose tolerance associated with lower plasma insulin levels. The acute metabolic effects of UCN2 were not mediated by SKM Gs signaling.Conclusion: Selective activation of Gs signaling in SKM causes an acute increase in blood glucose levels. However, acute in vivo stimulation of endogenous Gs-coupled receptors enriched in SKM has only a limited impact on whole-body glucose homeostasis, most likely due to the fact that these receptors are also expressed by pancreatic islets where they modulate insulin release.
AB - Objective: The goal of this study was to determine the glucometabolic effects of acute activation of Gs signaling in skeletal muscle (SKM) in vivo and its contribution to whole-body glucose homeostasis.Methods: To address this question, we studied mice that express a Gs-coupled designer G protein-coupled receptor (Gs-DREADD or GsD) selectively in skeletal muscle. We also identified two Gs-coupled GPCRs that are endogenously expressed by SKM at relatively high levels (β2-adrenergic receptor and CRF2 receptor) and studied the acute metabolic effects of activating these receptors in vivo by highly selective agonists (clenbuterol and urocortin 2 (UCN2), respectively).Results: Acute stimulation of GsD signaling in SKM impaired glucose tolerance in lean and obese mice by decreasing glucose uptake selectively into SKM. However, the acute metabolic effects following agonist activation of β2-adrenergic and, potentially, CRF2 receptors appear primarily mediated by altered insulin release. Clenbuterol injection improved glucose tolerance by increasing insulin secretion in lean mice. In SKM, clenbuterol stimulated glycogen breakdown. UCN2 injection resulted in decreased glucose tolerance associated with lower plasma insulin levels. The acute metabolic effects of UCN2 were not mediated by SKM Gs signaling.Conclusion: Selective activation of Gs signaling in SKM causes an acute increase in blood glucose levels. However, acute in vivo stimulation of endogenous Gs-coupled receptors enriched in SKM has only a limited impact on whole-body glucose homeostasis, most likely due to the fact that these receptors are also expressed by pancreatic islets where they modulate insulin release.
KW - Faculty of Science
KW - Skeletal muscle
KW - GPCR
KW - G protein
KW - DREADD
KW - Clenbuterol
KW - Urocortin 2
KW - Glucose homeostasis
U2 - 10.1016/j.molmet.2021.101415
DO - 10.1016/j.molmet.2021.101415
M3 - Journal article
C2 - 34883278
VL - 55
JO - Molecular Metabolism
JF - Molecular Metabolism
SN - 2212-8778
M1 - 101415
ER -
ID: 286994689