Abstract
Human immunodeficiency virus (HIV)-infected patients with lipodystrophy have decreased insulin-stimulated glucose uptake. Both endurance and resistance training improve insulin-stimulated glucose uptake in skeletal muscle of HIV-infected patients, but the mechanisms are unknown. This study aims to identify the molecular pathways involved in the beneficial effects of training on insulin-stimulated glucose uptake in skeletal muscle of HIV-infected patients. Eighteen sedentary male HIV-infected patients underwent a 16 week supervised training intervention, either resistance or strength training. Euglycemic–hyperinsulinemic clamps with muscle biopsies were performed before and after the training interventions. Fifteen age- and body mass index (BMI)-matched HIV-negative men served as a sedentary baseline group. Phosphorylation and total protein expression of insulin signaling molecules as well as glycogen synthase (GS) activity were analyzed in skeletal muscle biopsies in relation to insulin stimulation before and after training. HIV-infected patients had reduced basal and insulin-stimulated GS activity (%fractional velocity, [FV]) as well as impaired insulin-stimulated Aktthr308 phosphorylation. Despite improving insulin-stimulated glucose uptake, neither endurance nor strength training changed the phosphorylation status of insulin signaling proteins or affected GS activity. However; endurance training markedly increased the total Akt protein expression, and both training modalities increased hexokinase II (HKII) protein. HIV-infected patients with lipodystrophy have decreased insulin-stimulated glucose uptake in skeletal muscle and defects in insulin-stimulated phosphorylation of Aktthr308. Endurance and strength training increase insulin-stimulated glucose uptake in these patients, and the muscular training adaptation is associated with improved capacity for phosphorylation of glucose by HKII, rather than changes in markers of insulin signaling to glucose uptake or glycogen synthesis.
Highlights
Human immunodeficiency virus (HIV)-infected patients are treated with highly active combination antiretroviral therapy (HAART), which as a side effect leads to development of lipodystrophy
We have previously shown that lipodystrophic patients with HIV have a markedly decreased insulin-stimulated glucose disposal compared to nonlipodystrophic HIVnegative controls, but that supervised, intensive endurance and strength training in HIV-infected patients can restore the insulin-stimulated glucose uptake (Lindegaard et al 2008)
By using muscle biopsies from the same cohort, this study further investigates the molecular mechanisms underlying the decreased insulin sensitivity in skeletal muscle of HIV-infected patients and the possible proteins involved in the beneficial effects of exercise training on insulin sensitivity
Summary
Human immunodeficiency virus (HIV)-infected patients are treated with highly active combination antiretroviral therapy (HAART), which as a side effect leads to development of lipodystrophy. Defective oxidative glucose disposal in HIV-infected patients is caused by impaired glucose transport and phosphorylation (Behrens et al 2002), suggesting defects in glucose phosphorylating enzymes like hexokinase II (HKII). In both normal and diabetic subjects, storage of glucose as muscle glycogen accounts for the majority of the nonoxidative glucose disposal and for most of the total body glucose uptake during insulin infusion (Shulman et al 1990). The reduced nonoxidative glucose disposal in patients with HIV-associated lipodystrophy is believed to reflect impaired glycogen synthesis (Andersen et al 2003; Haugaard et al 2005), and molecular defects at the level of glycogen synthase (GS), glycogen synthase kinase (GSK)-3, and Akt have been demonstrated in skeletal muscle of patients with HIV-associated lipodystrophy (Haugaard et al 2005)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
