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Acta Physiol (Oxf). 2019 Jun;226(2):e13251. doi: 10.1111/apha.13251. Epub 2019 Jan 30.

An accumulation of muscle macrophages is accompanied by altered insulin sensitivity after reduced activity and recovery.

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Departments of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah.
University of Utah School of Medicine, Salt Lake City, Utah.
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah.
Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah.



Mechanisms underlying physical inactivity-induced insulin resistance are not well understood. In addition to a role in muscle repair, immune cell populations such as macrophages may regulate insulin sensitivity.


The aim of this study was to examine if the dynamic changes in insulin sensitivity during and after recovery from reduced physical activity corresponded to changes in skeletal muscle macrophages.


In this prospective clinical study, we collected muscle biopsies from healthy older adults (70 ± 2 years, n = 12) before and during a hyperinsulinaemic-euglycaemic clamp and this occurred before (PRE) and after 2-week reduced physical activity (RA), and following 2-week of recovery (REC). Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), skeletal muscle mRNA expression of inflammatory markers, and immunofluorescent quantification of skeletal muscle macrophages, myofibre-specific satellite cell and capillary content were assessed.


Insulin sensitivity was decreased following reduced activity and rebounded following recovery above PRE levels. We observed an increase (P < 0.01) in muscle macrophages (CD68+ CD206+ : 190 [55, 324]; CD11b+ CD206+ : 117 [28, 205]% change from PRE) and CD68 (2.4 [1.4, 3.4]-fold) and CCL2 (1.9 [1.3, 2.5]-fold) mRNA following RA concurrent with increased (P < 0.03) satellite cells (55 [6, 104]%) in slow-twitch myofibres. Moreover, the distance of satellite cells to the nearest capillary was increased 7.7 (1.7, 13.7) µm in fast-twitch myofibres at RA (P = 0.007). Changes in macrophages were positively associated with increased insulin sensitivity following RA (R > 0.57, P < 0.05).


These findings suggested that a dynamic response of skeletal muscle macrophages following acute changes in physical activity in healthy older adults is related to insulin sensitivity.


capillaries; immune; injury; insulin resistance; step reduction


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