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|Title:||Skeletal muscle JNK activity after acute resistive exercise in elder adults with T2D: Metabolic and clinical correlates|
|Keywords:||JNK, exercise, metabolic syndrome, insulin resistance|
|Publisher:||University of Sydney.|
|Abstract:||Objective This study describes the results of the baseline sub-study of a randomized double-blind, sham-exercise controlled trial designed to assess the efficacy of power training in older adults with type 2 diabetes. The primary purpose of this sub-study was to define the state of total and activated JNK in skeletal muscle which had been exposed to an acute resistive bout of exercise. In addition, metabolic and clinical characteristics were investigated in an attempt to explain the variance and the metabolic relevance of the JNK expression (total JNK, tJNK) and activation (ratio of phosphorylated/total JNK, p/tJNK) observed. We hypothsized that greater JNK expression and activation would be related to impaired health status, chronic inflammation, metabolic disturbance and insulin resistance in our cohort. We hypothsized that greater JNK expression and activation would be related to impaired health status (decreasing habitual exercise amount and burdens of diseases), chronic inflammation (increasing pro-inflammatory cytokines and decreasing anti-inflammatory cytokines), metabolic disturbance (disturbance of blood glucose and lipid regulation) and insulin resistance in our cohort. Methods Our cohort consisted of sedentary adults over 60 years of age with type 2 diabetes. The study recruited 103 participants from Aug 2006 to Dec 2009. Since the 50th participant completed theirassessments in Apr 2009 and this thesis was to be submitted in Aug 2010, it only included analysis of baseline data from the first 50 participants which were available at the time of submission. Insulin resistance was measured by homeostasis model assessment 2 (HOMA 2) computerized model; body composition was measured by computed tomography (CT) scan, bioelectric impedance analysis (BIA) and anthropometrics; glucose, insulin and serum cytokines (adiponectin, c-reactive protein (CRP) were measured by serum assays, factors related to the insulin signalling pathway obtained from skeletal muscle and subcutaneous adipose tissue biopsies (Insulin-like Growth Factor-1 (IGF-1), Tumour Necrosis Factor-α (TNFα), Interleukin 6 (IL-6), Heat Shock Protein 72 (HSP72), phospho-Jun N-terminal Kinase (pJNK) and total JNK (tJNK) in muscle, and Adiponetin, TNFα, IL-6 in adipose tissue) were measured by cytokine assays and Western Blot. The secondary outcomes, including health status, medications, physical performance and quality of life, were assessed by validated questionnaires. Results 35 of the 50 subjects had baseline measures of skeletal muscle JNK. As hypothesized, higher JNK was related or had the tendency to related to potentially poorer health status: number of medications/day(r=0.304, 0.081) and lower habitual physical activity (r=-0.333, p=0.055). Similarly, the relationships we found between total and activated JNK and anti-inflammatory/metabolic factors supported our hypotheses: higher tJNK was related to lower serum (r=-0.364, p=0.057) and adipose tissue (r=-0.465, p=0.060) HMW/adiponectin ratios, and higher p/tJNK was related to higher skeletal muscle IL-6 (rho=0.644, p<0.001), lower serum total (r=-0.336, p=0.081) and HMW adiponectin (r=-0.504, p=0.006), and lower HOMA β cell function (r=-0.332, p=0.055). By contrast, the relationships we found between JNK and systemic pro-inflammatory and local anabolic factors were inconsistent with our hypothesis. Specifically, higher tJNK was related to lower serum CRP (r=-0.457,p=0.015) and higher skeletal muscle IGF-1(r=0.641, p<0.001). Also contrary to our expectations, higher p/tJNK was related to lower serum total cholesterol (r=-0.059, p<0.001) and LDL (r=-0.401, p=0.016). Conclusion This was the first study to describe activated and total skeletal muscle JNK expression after acute resistive exercise in older adults with type 2 diabetes, and the first study to analyze potential correlations between skeletal muscle JNK and other aspects of health status, metabolism, and inflammation in this cohort. As hypothesized, higher JNK was related to more impaired health status (age, inactivity) and inversely related to anti-inflammatory adiponectin and HOMA2 β cell function. Unexpectedly, however, higher JNK was related to higher skeletal muscle IGF-1 and inversely related to CRP, serum total cholesterol and LDL. Additional studies are warranted to investigate whether chronic exercise training in type 2 diabetes alters the expression and activation of JNK, and to determine whether beneficial adaptations in JNK may explain a portion of the variance in exercise-related metabolic benefits in this cohort.|
|Rights and Permissions:||The author retains copyright of this thesis.|
|Type of Work:||Masters Thesis|
|Appears in Collections:||Sydney Digital Theses (Open Access)|
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