Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion

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Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion. / Han, Xiuqing; Raun, Steffen Henning; Carlsson, Michala; Sjøberg, Kim Anker; Henriquez-Olguín, Carlos; Ali, Mona; Lundsgaard, Annemarie; Fritzen, Andreas Mæchel; Møller, Lisbeth Liliendal Valbjørn; Li, Zhen; Li, Jinwen; Jensen, Thomas Elbenhardt; Kiens, Bente; Sylow, Lykke.

I: Metabolism - Clinical and Experimental, Bind 105, 154169, 2020.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Han, X, Raun, SH, Carlsson, M, Sjøberg, KA, Henriquez-Olguín, C, Ali, M, Lundsgaard, A, Fritzen, AM, Møller, LLV, Li, Z, Li, J, Jensen, TE, Kiens, B & Sylow, L 2020, 'Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion', Metabolism - Clinical and Experimental, bind 105, 154169. https://doi.org/10.1016/j.metabol.2020.154169

APA

Han, X., Raun, S. H., Carlsson, M., Sjøberg, K. A., Henriquez-Olguín, C., Ali, M., ... Sylow, L. (2020). Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion. Metabolism - Clinical and Experimental, 105, [154169]. https://doi.org/10.1016/j.metabol.2020.154169

Vancouver

Han X, Raun SH, Carlsson M, Sjøberg KA, Henriquez-Olguín C, Ali M o.a. Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion. Metabolism - Clinical and Experimental. 2020;105. 154169. https://doi.org/10.1016/j.metabol.2020.154169

Author

Han, Xiuqing ; Raun, Steffen Henning ; Carlsson, Michala ; Sjøberg, Kim Anker ; Henriquez-Olguín, Carlos ; Ali, Mona ; Lundsgaard, Annemarie ; Fritzen, Andreas Mæchel ; Møller, Lisbeth Liliendal Valbjørn ; Li, Zhen ; Li, Jinwen ; Jensen, Thomas Elbenhardt ; Kiens, Bente ; Sylow, Lykke. / Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion. I: Metabolism - Clinical and Experimental. 2020 ; Bind 105.

Bibtex

@article{d8db1dc9849c4c418b20853a6f90f082,
title = "Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion",
abstract = "Background: Redirecting glucose from skeletal muscle and adipose tissue, likely benefits the tumor's energy demand to support tumor growth, as cancer patients with type 2 diabetes have 30{\%} increased mortality rates. The aim of this study was to elucidate tissue-specific contributions and molecular mechanisms underlying cancer-induced metabolic perturbations.Methods: Glucose uptake in skeletal muscle and white adipose tissue (WAT), as well as hepatic glucose production, were determined in control and Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mice using isotopic tracers. Skeletal muscle microvascular perfusion was analyzed via a real-time contrast-enhanced ultrasound technique. Finally, the role of fatty acid turnover on glycemic control was determined by treating tumor-bearing insulin-resistant mice with nicotinic acid or etomoxir.Results: LLC tumor-bearing mice displayed reduced insulin-induced blood-glucose-lowering and glucose intolerance, which was restored by etomoxir or nicotinic acid. Insulin-stimulated glucose uptake was 30-40{\%} reduced in skeletal muscle and WAT of mice carrying large tumors. Despite compromised glucose uptake, tumor-bearing mice displayed upregulated insulin-stimulated phosphorylation of TBC1D4Thr642 (+18{\%}), AKTSer474 (+65{\%}), and AKTThr309 (+86{\%}) in muscle. Insulin caused a 70{\%} increase in muscle microvascular perfusion in control mice, which was abolished in tumor-bearing mice. Additionally, tumor-bearing mice displayed increased (+45{\%}) basal (not insulin-stimulated) hepatic glucose production.Conclusions: Cancer can result in marked perturbations on at least six metabolically essential functions; i) insulin's blood-glucose-lowering effect, ii) glucose tolerance, iii) skeletal muscle and WAT insulin-stimulated glucose uptake, iv) intramyocellular insulin signaling, v) muscle microvascular perfusion, and vi) basal hepatic glucose production in mice. The mechanism causing cancer-induced insulin resistance may relate to fatty acid metabolism.",
keywords = "Faculty of Science, Lewis lung carcinoma, Cancer, Insulin resistance, Glycaemic regulation, Microvascular perfusion",
author = "Xiuqing Han and Raun, {Steffen Henning} and Michala Carlsson and Sj{\o}berg, {Kim Anker} and Carlos Henriquez-Olgu{\'i}n and Mona Ali and Annemarie Lundsgaard and Fritzen, {Andreas M{\ae}chel} and M{\o}ller, {Lisbeth Liliendal Valbj{\o}rn} and Zhen Li and Jinwen Li and Jensen, {Thomas Elbenhardt} and Bente Kiens and Lykke Sylow",
note = "Copyright {\circledC} 2020 Elsevier Inc. All rights reserved.",
year = "2020",
doi = "10.1016/j.metabol.2020.154169",
language = "English",
volume = "105",
journal = "Metabolism",
issn = "0026-0495",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion

AU - Han, Xiuqing

AU - Raun, Steffen Henning

AU - Carlsson, Michala

AU - Sjøberg, Kim Anker

AU - Henriquez-Olguín, Carlos

AU - Ali, Mona

AU - Lundsgaard, Annemarie

AU - Fritzen, Andreas Mæchel

AU - Møller, Lisbeth Liliendal Valbjørn

AU - Li, Zhen

AU - Li, Jinwen

AU - Jensen, Thomas Elbenhardt

AU - Kiens, Bente

AU - Sylow, Lykke

N1 - Copyright © 2020 Elsevier Inc. All rights reserved.

PY - 2020

Y1 - 2020

N2 - Background: Redirecting glucose from skeletal muscle and adipose tissue, likely benefits the tumor's energy demand to support tumor growth, as cancer patients with type 2 diabetes have 30% increased mortality rates. The aim of this study was to elucidate tissue-specific contributions and molecular mechanisms underlying cancer-induced metabolic perturbations.Methods: Glucose uptake in skeletal muscle and white adipose tissue (WAT), as well as hepatic glucose production, were determined in control and Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mice using isotopic tracers. Skeletal muscle microvascular perfusion was analyzed via a real-time contrast-enhanced ultrasound technique. Finally, the role of fatty acid turnover on glycemic control was determined by treating tumor-bearing insulin-resistant mice with nicotinic acid or etomoxir.Results: LLC tumor-bearing mice displayed reduced insulin-induced blood-glucose-lowering and glucose intolerance, which was restored by etomoxir or nicotinic acid. Insulin-stimulated glucose uptake was 30-40% reduced in skeletal muscle and WAT of mice carrying large tumors. Despite compromised glucose uptake, tumor-bearing mice displayed upregulated insulin-stimulated phosphorylation of TBC1D4Thr642 (+18%), AKTSer474 (+65%), and AKTThr309 (+86%) in muscle. Insulin caused a 70% increase in muscle microvascular perfusion in control mice, which was abolished in tumor-bearing mice. Additionally, tumor-bearing mice displayed increased (+45%) basal (not insulin-stimulated) hepatic glucose production.Conclusions: Cancer can result in marked perturbations on at least six metabolically essential functions; i) insulin's blood-glucose-lowering effect, ii) glucose tolerance, iii) skeletal muscle and WAT insulin-stimulated glucose uptake, iv) intramyocellular insulin signaling, v) muscle microvascular perfusion, and vi) basal hepatic glucose production in mice. The mechanism causing cancer-induced insulin resistance may relate to fatty acid metabolism.

AB - Background: Redirecting glucose from skeletal muscle and adipose tissue, likely benefits the tumor's energy demand to support tumor growth, as cancer patients with type 2 diabetes have 30% increased mortality rates. The aim of this study was to elucidate tissue-specific contributions and molecular mechanisms underlying cancer-induced metabolic perturbations.Methods: Glucose uptake in skeletal muscle and white adipose tissue (WAT), as well as hepatic glucose production, were determined in control and Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mice using isotopic tracers. Skeletal muscle microvascular perfusion was analyzed via a real-time contrast-enhanced ultrasound technique. Finally, the role of fatty acid turnover on glycemic control was determined by treating tumor-bearing insulin-resistant mice with nicotinic acid or etomoxir.Results: LLC tumor-bearing mice displayed reduced insulin-induced blood-glucose-lowering and glucose intolerance, which was restored by etomoxir or nicotinic acid. Insulin-stimulated glucose uptake was 30-40% reduced in skeletal muscle and WAT of mice carrying large tumors. Despite compromised glucose uptake, tumor-bearing mice displayed upregulated insulin-stimulated phosphorylation of TBC1D4Thr642 (+18%), AKTSer474 (+65%), and AKTThr309 (+86%) in muscle. Insulin caused a 70% increase in muscle microvascular perfusion in control mice, which was abolished in tumor-bearing mice. Additionally, tumor-bearing mice displayed increased (+45%) basal (not insulin-stimulated) hepatic glucose production.Conclusions: Cancer can result in marked perturbations on at least six metabolically essential functions; i) insulin's blood-glucose-lowering effect, ii) glucose tolerance, iii) skeletal muscle and WAT insulin-stimulated glucose uptake, iv) intramyocellular insulin signaling, v) muscle microvascular perfusion, and vi) basal hepatic glucose production in mice. The mechanism causing cancer-induced insulin resistance may relate to fatty acid metabolism.

KW - Faculty of Science

KW - Lewis lung carcinoma

KW - Cancer

KW - Insulin resistance

KW - Glycaemic regulation

KW - Microvascular perfusion

U2 - 10.1016/j.metabol.2020.154169

DO - 10.1016/j.metabol.2020.154169

M3 - Journal article

C2 - 31987858

VL - 105

JO - Metabolism

JF - Metabolism

SN - 0026-0495

M1 - 154169

ER -

ID: 237512725