We previously reported that insulin resistance in skeletal muscle of obese individuals was associated with decreases in insulin signal transduction and tyrosine kinase activity of the insulin receptor. Herein is reviewed the recently published data supporting the hypothesis that protein kinase C (PKC) phosphorylates the insulin receptor on serine/threonine residues to decrease tyrosine kinase activity and cause insulin resistance. Treatment of insulin receptors from obese subjects with alkaline phosphatase restored tyrosine kinase activity, suggesting that the reduced activity was a result of hyperphosphorylation of the receptor. Incubating human muscle fiber strips with PKC inhibitors restored insulin action in muscle of obese patients, while activating PKC with a phorbol ester caused insulin resistance in muscle from lean control patients. The beta isoform of PKC was elevated in muscle of obese, insulin-resistant patients. These data are consistent with the hypothesis that elevated PKC activity may cause insulin resistance by phosphorylating the insulin receptor to decrease tyrosine kinase activity.
Kyu-Jin Lee, Yun-A. Shin, Kyoung-Young Lee, Tae-Won Jun and Wook Song
The purpose of this study was to assess differences in the levels of plasma visfatin among female adolescents and changes in plasma visfatin and insulin resistance in obese female adolescents after 12 wk of aerobic exercise training. Twenty normal-weight female students (body-mass index [BMI] <22.9 kg/m2 and body fat ≤29.9) and 18 obese female students (BMI ≥25 kg/m2 and body fat ≥30%) participated in this study. Eleven obese students were assigned to an exercise group and completed a 12-wk aerobic exercise-training program that included four 40- to 50-min sessions per wk with an energy expenditure of 300–400 kcal/d. Seven obese students were assigned to a control group that received no exercise sessions or dietary restriction. The plasma visfatin levels of obese female adolescents were significantly higher (p < .05) than those of the normal-weight female adolescents. The plasma visfatin levels (294.00 ± 124.74 ng/ml to 185.55 ± 67.30 ng/ml, p < .01) and insulin resistance (p < .05) were significantly reduced after 12 wk of aerobic exercise. The results suggest that aerobic exercise resulting in an energy expenditure of 1,200–1,600 kcal/wk for 12 wk decreases plasma visfatin and insulin resistance in obese female adolescents.
Bumsoo Ahn, Robert McMurray and Joanne Harrell
The relationship between insulin resistance (HOMA-IR), percent body fat, and aerobic fitness (VO2max per unit fat free mass; mL/kgFFM/min) was examined in 1,710 children. Percent body fat was estimated from sum of skinfolds, and VO2max was estimated from submaximal cycle ergometer tests. Overnight fasting blood samples were obtained. VO2max (mL/kgFFM/min) and percent body fat were correlated with HOMA-IR (r=-0.076, p < .002; r=.420, p < .001, respectively); as was VO2max in units of mL/kg/min (r=-0.264, p < .001). When VO2max in mL/kg/min was used, a progressive increase in HOMA-IR was found with decreasing fitness (p < .05). However, when mL/kgFFM/min was used, HOMA-IR scores remained similar between moderate-fit and low-fit group. The stronger association between aerobic fitness (mL/kg/min) and HOMA-IR is partially due to the significant association of fat mass to HOMA-IR. Therefore, our recommendation is to express aerobic fitness in units of mL/kgFFM/min to eliminate the confounding factor of adiposity and better understand the influence of muscle on insulin resistance.
Chiao-Nan Chen, Lee-Ming Chuang, Mallikarjuna Korivi and Ying-Tai Wu
This study investigated the differences in exercise self-efficacy, compliance, and effectiveness of home-based exercise in individuals with and without metabolic syndrome (MetS).
One hundred and ten individuals at risk for diabetes participated in this study. Subjects were categorized into individuals with MetS and individuals without MetS. Metabolic risk factors and exercise self-efficacy were evaluated for all subjects before and after 3 months of home-based exercise. Univariate analysis of variance was used to compare the effectiveness of a home-based exercise program between individuals with and without MetS.
The home-based exercise program improved body mass index and lipid profile in individuals at risk for diabetes, regardless of MetS status at baseline. Individuals without MetS had higher exercise self-efficacy at baseline and performed greater exercise volume compared with individuals with MetS during the intervention. The increased exercise volume in individuals without MetS may contribute to their better control of insulin resistance than individuals with MetS. Furthermore, baseline exercise self-efficacy was correlated with exercise volume executed by subjects at home.
We conclude that home-based exercise programs are beneficial for individuals at risk for diabetes. However, more intensive and/or supervised exercise intervention may be needed for those with MetS.
Joan Khoo, Subbiah Dhamodaran, Dan-Dan Chen, Siew-Yoon Yap, Richard Yuan-Tud Chen and Roger Ho-Heng Tian
The adipokines chemerin and adiponectin are reciprocally related in the pathogenesis of insulin resistance and inflammation in obesity. Weight loss increases adiponectin and reduces chemerin, insulin resistance, and inflammation, but the effects of caloric restriction and physical activity are difficult to separate in combined lifestyle modification. We compared effects of diet- or exercise-induced weight loss on chemerin, adiponectin, insulin resistance, and inflammation in obese men. Eighty abdominally obese Asian men (body mass index [BMI] ≥ 30 kg/m2, waist circumference [WC] ≥ 90 cm, mean age 42.6 years) were randomized to reduce daily intake by ~500 kilocalories (n = 40) or perform moderate-intensity aerobic and resistance exercise (200–300 min/week) (n = 40) to increase energy expenditure by a similar amount for 24 weeks. The diet and exercise groups had similar decreases in energy deficit (−456 ± 338 vs. −455 ± 315 kcal/day), weight (−3.6 ± 3.4 vs. −3.3 ± 4.6 kg), and WC (−3.4 ± 4.4 vs. −3.6 ± 3.2 cm). The exercise group demonstrated greater reductions in fat mass (−3.9 ± 3.5 vs. −2.7 ± 5.3 kg), serum chemerin (−9.7 ± 11.1 vs. −4.3 ± 12.4 ng/ml), the inflammatory marker high-sensitivity C-reactive protein (−2.11 ± 3.13 vs. −1.49 ± 3.08 mg/L), and insulin resistance as measured by homeostatic model assessment (−2.45 ± 1.88 vs. −1.38 ± 3.77). Serum adiponectin increased only in the exercise group. Exercise-induced fat mass loss was more effective than dieting for improving adipokine profile, insulin resistance, and systemic inflammation in obese men, underscoring metabolic benefits of increased physical activity.
Anita T. Cote, Angela M. Devlin and Constadina Panagiotopoulos
Second-generation antipsychotic (SGA) medications, used to treat youth for a wide-range of mental health conditions, are associated with excessive weight gain and other comorbidities, placing these individuals at high risk for cardiovascular disease. Little is known about the effect of physical activity (PA) on cardiovascular risk in these children. Anthropometrics, fasting blood sample and self-report PA were obtained in 386 children diagnosed with mental health conditions (6–18 y). PA was classified as below (<60 min/day) or meets (>60 min/day) current recommended guidelines for daily PA in children. SGA-treated (n = 166) and SGA-naive (n = 220) were compared in the analysis. The SGA-treated children had higher (p < .05) BMI z-score, waist-to-height ratio, fasting glucose, and LDL-cholesterol than SGA-nai’ve children. Waist circumference, waist-to-height ratio, HDL cholesterol, fasting insulin, and HOMA-IR were significantly different by PA status. After adjusting for SGA-treatment duration, sex, age, and ethnicity, higher PA was associated with lower insulin resistance (HOMA-IR) in SGA-treated (mean, 95% CI; below vs. meets: 2.10 [1.84, 2.37] vs. 1.59 [1.37, 1.81], p = .046) but not in SGA-naive (1.70 [1.47, 1.94] vs 1.55 [1.35, 1.75], p = .707) children. Upon initial screening, SGA-treated children that reported meeting the minimal recommendations for daily PA displayed lower measures of adiposity and improved insulin resistance.
Marc S. Mitchell, Catherine A. Gaul, Patti-Jean Naylor and Constadina Panagiotopoulos
The aim of this study was to explore the relationship between insulin resistance (IR) and objectively measured habitual moderate-to-vigorous physical activity (MVPA) in First Nations youth. A cross-sectional study was conducted in 2 rural villages in northern British Columbia, Canada. Thirty-nine healthy youth (16 males and 23 females; age = 11.8yrs ± 2.2; range = 8.8–18.5yrs) participated. PA was measured with ActiGraph GT1M accelerometers. The homeostasis model assessment estimate of IR (HOMA-IR) was used to define IR. Duration of MVPA was inversely related to HOMA-IR (r=−.44, p < .01). From the regression model, 30 min of habitual MVPA corresponded to HOMA-IR levels that were 15% lower. In conclusion, these findings suggest that active First Nations youth have lower HOMA-IR values.
Sheri J. Hartman, Catherine R. Marinac, Lisa Cadmus-Bertram, Jacqueline Kerr, Loki Natarajan, Suneeta Godbole, Ruth E. Patterson, Brittany Morey and Dorothy D. Sears
evidence in noncancer populations suggests that breaking up sedentary time is positively associated with improved health outcomes. 13 – 16 Excessive sedentary time is associated with systemic inflammation [generally assessed using C-reactive protein (CRP)] and insulin resistance [as measured using the
Yuko Gando, Haruka Murakami, Ryoko Kawakami, Noriko Tanaka, Kiyoshi Sanada, Izumi Tabata, Mitsuru Higuchi and Motohiko Miyachi
It is unclear whether light physical activity is beneficially associated with insulin resistance, similar to moderate and/or vigorous physical activity. This cross-sectional study was performed to determine the relationship between the amount of light physical activity, as determined with a triaxial accelerometer, and insulin resistance.
A total of 807 healthy men and women participated in this study. Physical activity was measured using a triaxial accelerometer worn for 28 days and summarized as light intensity (1.1–2.9 METs) or moderate to vigorous intensity (≥ 3.0 METs). Insulin resistance was evaluated by HOMA_R (FPG [mg/dL] × IRI [μU/mL]/405).
The daily time spent in light physical activity was inversely associated with HOMA_R (r = –0.173, P < 0.05). After adjustment for confounders, the association between light physical activity and HOMA_R remained statistically significant (β = –0.119, P < .05). Light physical activity remained significantly associated with HOMA_R following further adjustment for moderate to vigorous intensity activity (β = –0.125, P < .05). Similar results were observed when light physical activity was modeled as quartiles, especially in elderly women.
These cross-sectional data suggest that light-intensity physical activity is beneficially associated with insulin resistance in elderly Japanese women.
Yanmei Niu, Hong Yuan and Li Fu
Insulin resistance (IR) is a common pathophysiological feature of Type 2 diabetes. Although the mechanisms leading to IR are still elusive, evidence has shown that aerobic exercise can reverse this process. To investigate the effects of aerobic exercise on IR, the authors created an IR animal model by feeding C57BL/6 mice a high-fat diet for 8 wk. They then compared the effect of 6 wk of treadmill training (60 min/d) at 75% VO2max on mice in normal-diet (NE) and high-fat-diet (HE) groups with their sedentary control groups. Levels of skeletal-muscle AMPKα (AMP-activated protein kinase α), ACC (acetyl-CoA carboxylases), and CPT1 (carnitine palmitoyltransferase 1) mRNA and AMPKα, pAMPK-Thr172, ACC, pACC-Ser79, and CPT1 protein expressions were analyzed. In addition, fasting serum levels of insulin, triglyceride, and cholesterol were measured. The results demonstrate that 6 wk of exercise increased AMPKα mRNA expression by 11% and 25 % (p < .01) in the NE and HE groups, respectively, and AMPKα protein expression by 37.9% and 20.1% (p < .01) in NE and HE compared with their sedentary control. In addition, ACC mRNA and protein expressions declined, whereas CPT1 mRNA and protein expressions were elevated in both exercise groups compared with sedentary control groups. In addition, pAMPK-Thr172 and pACC-Ser79 expression increased significantly in the NE and HE groups compared with sedentary control groups. In conclusion, our results demonstrate that 6 wk of aerobic exercise can effectively ameliorate IR by increasing the expression of AMPKα and pAMPK-Thr172, thereby activating the key enzymes that facilitate lipid metabolism.