Rac1 muscle knockout exacerbates the detrimental effect of high-fat diet on insulin-stimulated muscle glucose uptake independently of Akt

The Journal of Physiology
Steffen H RaunLykke Sylow

Abstract

The actin cytoskeleton regulating GTPase, Rac1, is a novel player in insulin-stimulated glucose uptake in muscle in vivo. High-fat diet (HFD) exacerbates muscle insulin resistance in Rac1 muscle knockout (mKO) mice. Muscle Rac1 KO protects against HFD-induced insulin resistance in fat tissue indicating tissue cross-talk. A fatty diet markedly reduces insulin clearance in mice. Insulin resistance and perturbations in glucose metabolism underpin common lifestyle diseases such as type 2 diabetes and obesity. Insulin resistance in muscle is characterized by compromised activity of the GTPase, Ras-related C3 Botulinum toxin substrate 1 (Rac1), yet the role of Rac1 in insulin-stimulated glucose uptake in vivo and diet-induced insulin resistance is unknown. Inducible muscle-specific Rac1 knockout (Rac1 mKO) and wild type (WT) littermate mice were either fed a chow or a 60% high-fat diet (HFD). Insulin-stimulated 2-deoxy-glucose uptake, intracellular signalling, protein expression, substrate utilization, and glucose and insulin tolerance were assessed. In chow-fed mice, in vivo insulin-stimulated glucose uptake was reduced in triceps, soleus and gastrocnemius muscles from Rac1 mKO mice. HFD-induced whole body insulin resistance was exa...Continue Reading

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Citations

May 19, 2018·The Journal of Physiology·Stephan van Vliet, Bettina Mittendorfer
Aug 31, 2018·The Journal of Physiology·Daniel M Marko, Hesham Shamshoum
May 12, 2019·Cells·Lisbeth Liliendal Valbjørn MøllerLykke Sylow
Dec 29, 2018·Physiological Reports·Harrison D StierwaltSean A Newsom
Oct 8, 2019·Antioxidants & Redox Signaling·Carlos Henríquez-OlguínThomas E Jensen
Aug 14, 2019·Journal of Cachexia, Sarcopenia and Muscle·Xiuqing HanLykke Sylow
Jun 17, 2020·Journal of Cellular Physiology·Rafael A CasusoJesús R Huertas
Mar 28, 2020·Nature Communications·Steffen H RaunLykke Sylow
Nov 28, 2020·Journal of Cellular Physiology·Irena AudzeyenkaAgnieszka Piwkowska
Nov 10, 2021·The Biochemical Journal·Erik A RichterMark Hargreaves

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