Exercise Improves Insulin Sensitivity Research Articles

Optimizing Polycystic Ovarian Disorder (PCOD) Treatment with Personalized Lifestyle and Nutrition Strategies

Introduction: Polycystic Ovarian Disorder (PCOD) is a prevalent endocrine illness in women of reproductive age. It has hormonal abnormalities, irregular menstrual cycles and tiny ovarian cysts. Lifestyle and food affect PCOD development and maintenance, coupled with medical therapies. Lifestyle, diet and PCOD are interconnected in this thorough assessment. Methodology: The evaluation comprises PCOD, lifestyle, diet, exercise, stress management and nutrition research published between January 1, 2000 and May 1, 2023. Result: PCOS management requires lifestyle changes including frequent exercise, a healthy weight, nutritious diet and no cigarettes. While lifestyle modifications cannot substitute medical care, they improve well-being. Low-GI, ketogenic and omega-3 fatty acid diets may reduce insulin resistance and PCOS symptoms. Eating no Saturated Fats (SFAs) is also important. Exercise improves insulin sensitivity, but high-intensity sessions improve cardiorespiratory fitness, insulin resistance and body composition more. We propose intense aerobic and strength training. PCOS might worsen insulin resistance due to sleep disruptions. Getting enough sleep is important for metabolism. PCOS sufferers may have reduced melatonin, which regulates the body’s 24-hour schedule, underlining the significance of sleep. Vitamin D, inositol, folate, B-group vitamins, vitamin K and vitamin E may improve insulin sensitivity and hormonal balance. Vitamins including bioflavonoids, carnitine and alpha-lipoic acid and minerals like chromium picolinate, calcium, magnesium, selenium and zinc may also help PCOS sufferers. More study is required to prove their effectiveness. Conclusion: PCOD is complicated and needs comprehensive treatment. Lifestyle, food and medical therapies should be combined for best outcomes. Healthcare practitioners and PCOD patients must collaborate to create tailored lifestyle, diet and supplement recommendations. Improve these remedies for the PCOD community with further study.

Pre-transplant Exercise May Improve Glycemic Outcomes After Marginal Islet Mass Transplant in Type 1 Diabetes

Pancreatic islet transplantation (ITx) is a treatment option for restoring glucose balance in some individuals with type 1 diabetes (T1D). However, the need for multiple donors to achieve insulin independence is an obstacle preventing ITx from becoming the standard of care in T1D. Exercise improves insulin sensitivity, increases insulin-independent glucose uptake, shortens recovery from surgery and decreases surgery-related complication risk. We tested the hypothesis that pre-transplant exercise training (RUN, n=7) would improve blood glucose outcomes in an STZ-induced T1D rat model having undergone syngeneic ITx with marginal islet mass (7000 IEQ/kg) compared to similarly-treated sedentary controls (SIT, n=6).

Interactive effects of acute exercise and carbohydrate-energy replacement on insulin sensitivity in healthy adults.

This study investigated whether carbohydrate-energy replacement immediately after prolonged endurance exercise attenuates insulin sensitivity the following morning, and whether exercise improves insulin sensitivity the following morning independent of an exercise-induced carbohydrate deficit. Oral glucose tolerance and whole-body insulin sensitivity were compared the morning after 3 evening conditions, involving (1) treadmill exercise followed by a carbohydrate replacement drink (200 or 150g maltodextrin for males and females, respectively; CHO-replace); (2) treadmill exercise followed by a non-caloric, taste-matched placebo (CHO-deficit); or (3) seated rest with no drink provided (Rest). Treadmill exercise involved 90minutes at ∼80% age-predicted maximum heart rate. Seven males and 2 females (aged 23± 1years; body mass index 24.0± 2.7kg·m-2) completed all conditions in a randomised order. Matsuda index improved by 22% (2.2 [0.3, 4.0] au, p= 0.03) and HOMA2-IR improved by 10% (-0.04 [-0.08, 0.00] au, p= 0.04) in CHO-deficit versus CHO-replace, without corresponding changes in postprandial glycaemia. Outcomes were similar between Rest and other conditions. These data suggest that improvements to insulin sensitivity in healthy populations following acute moderate/vigorous intensity endurance exercise may be dependent on the presence of a carbohydrate-energy deficit. Novelty: Restoration of carbohydrate balance following acute endurance exercise attenuated whole-body insulin sensitivity. Exercise per se failed to enhance whole-body insulin sensitivity. Maximising or prolonging the post-exercise carbohydrate deficit may enhance acute benefits to insulin sensitivity.

Comparison of Short-Term Structured Exercise in Non-Over Weight and Overweight Subjects with Polycystic Ovarian Syndrome

Polycystic Ovarian Syndrome is one of the most common female endocrinological disorder which is a complex multifaceted heterogeneous disorder affecting approximately 5%-10% of respondents of reproductive age, endocrine and metabolic function. The patients with PCOS have elevated triglyceride and low-density lipoprotein (LPL) cholesterol levels and low high-density lipoprotein (HDL) cholesterol levels. Exercise combined Aerobic and Resistance exercise improves insulin sensitivity and glycaemic control, reduces abdominal fat in women and modified with diet is considered to be preferred as the first-line treatment for PCOS management with the primary goal to normalize serum androgen and to restore reproductive function. The aim of the study was to find the effect of comparison of short-term structured exercise in non-over weight and overweight subjects with Polycystic Ovarian Syndrome. This experimental study design with a total of 30 subjects were taken by simple random sampling method at Outpatient Physiotherapy Department, ACS Medial college and hospital, vellapanchavadi, chennai. The subjects included were those with secondary amenorrhoea, body hair growing on the chest, belly, face and around the nipples, decreased breast size irregular periods, male-like characteristics, enlargement of the clitoris, male-pattern baldness, acne, cysts on the ovaries, Overweight, skin tags, anxiety or depression, hoarseness of voice, dark or thick skin markings and creases around the armpits groin, neck and breasts, dandruff patches on skin on the neck, arm, breasts, thigh, pelvic pain, sleep apnea, age group with 18-25,unmarried women, BMI ranging between 18-25. The subjects excluded were those with diabetes, thyroid, adrenal or pituitary gland dysfunction obese women, undergoing medications, seizures, hypertension ,cardiac patients, psychological problems, fracture, Non co-operative patients, age group(<18 and >25),neurological problems ,low back ache, married women, pelvic inflammatory disease, urinary tract infection, recent abdominal surgery . The outcome measure is measured by (PCOSQ-50) questionnaire and BMI scale. Group-A consisted of Overweight subjects and Group-B consisted of Non-over weight subjects and both the groups received Aerobic and Resistance training along with dietary plans for 56 days with 3 sessions per week on consecutive days. The PCOSQ-50 questionnaire was used. Result On comparing the mean values of Group A and Group B among BMI and PCOSQ-50 Questionnaire Group A shows (23.16) and (100.91) which has the lower mean value of BMI and PCOS Q50 (100.9) is more effective than group B BMI (27.01) and PCOSQ-50 (109.8). Exercise along with dietary plan shows greater improvement among subjects in Group-A (Overweight) with polycystic ovarian syndrome than Group B.

Effects of a single bout of short-duration high-intensity and long-duration low-intensity exercise on insulin resistance and adiponectin/leptin ratio

ObjectivesModerate-intensity exercise improves insulin sensitivity, which may depend on the intensity, duration, and frequency of exercise. We examined the effects of a single bout of short-duration high-intensity exercise (HIE) and long-duration lowintensity exercise (LIE) on insulin sensitivity and the adiponectin/leptin ratio in individuals with different body mass indices (BMIs) who do not exercise regularly. MethodsWe enrolled 42 healthy volunteers aged 20–64 years and divided them into two groups based on BMI: BMI <24 kg/m2 and BMI ≥27 kg/m2. They were randomly assigned to either the short-duration (20 min) HIE (70%–80% heart rate reserve, HRR) or long-duration (60 min) LIE training groups (30%–40% HRR). Glucose, insulin, adiponectin, and leptin levels were assessed before training and at 0, 30, 60, and 120 min after training. ResultsWe finally analyzed 27 normal weight and 9 obese individuals. No significant differences were observed in the baseline information of both BMI groups. Homeostatic model assessment for insulin resistance significantly improved for both exercise patterns in the normal weight group and for the HIE pattern in the obese group (P < 0.01), whereas the adiponectin/leptin ratio increased significantly only among normal weight participants with the LIE intervention. ConclusionBoth exercise patterns in BMI <24 kg/m2 and BMI ≥27 kg/m2 benefit on insulin resistance. Therefore, people can choose the way they can fit to improve insulin resistance both short-duration high-intensity exercise and long-duration low-intensity exercise.

699-P: Association between Exercise Capacity and All-Cause Mortality in Taiwanese Adults

Background: Exercise improves insulin sensitivity, inhibits inflammatory cytokines, and reduces the risk of cardiovascular disease. But the effect of exercise capacity on all-cause mortality in Taiwanese adults has not been fully explored. Methods: We used data from the National Health Interview Survey and the National Health Insurance research database in Taiwan. Baseline participants’ characteristics including socioeconomic status and health behaviors were obtained by standardized face to face interviews in 2001, 2005, 2009, and 2013. Comorbidities were confirmed by National Health Insurance research database 2000-2016. Participants were followed up until December 31 2016. All-cause mortality was ascertained from the National Registration of Death. Kaplan-Meier curves and Cox proportional hazard analysis were used to evaluate the relationship between exercise capacity and all-cause mortality. Results: In total, 65,126 adults aged more than 18 years old were analyzed; 32,563 (50%) were male and with a mean (SD) age of 42.90 (16.17) years. Kaplan-Meier curves of all-cause mortality stratified by exercise capacity demonstrated significant findings (Log-rank P&amp;lt;0.01). Multivariate Cox regression analysis showed that those with higher exercise capacity had a significantly decreased risk of all-cause mortality, compared with those with no exercise habits (moderate exercise with 0-800 kcal/week HR = 0.78, 95% CI: 0.71-0.85, high exercise with more than 800 kcal/week HR = 0.73, 95% CI: 0.67-0.79) after adjusting for potential confounders. A significant trend (P for trend&amp;lt;0.01) was also noted. Conclusions: People with increased exercise capacity had a significant decreased risk of all-cause mortality. Further studies should investigate the type and dose of exercise that is most helpful for the general population to prolong life expectancy. Disclosure Y. Lai: None.

Exercise improves adiposopathy, insulin sensitivity and metabolic syndrome severity independent of intensity.

What is the central question of this study? What are the effects of work-matched continuous versus high-intensity interval training for 2weeks on adiposopathy and cardiometabolic risk in obese adults with prediabetes? What is the main finding and its importance? Independent of intensity, short-term exercise improves adiposopathy and insulin sensitivity. While both exercise intensities reduced fasting leptin concentrations and metabolic syndrome severity, only interval training elevated total adiponectin. In contrast to previous work, neither condition altered high-molecular weight adiponectin. Collectively, these data suggest that short-term exercise can improve adipokine profiles, which may aid in reducing cardiometabolic risk prior to clinically meaningful weight loss in adults with prediabetes. Individuals with prediabetes who are overweight and obese are at an increased risk of developing endocrine disruption of fat tissue, known as adiposopathy. While short-term exercise improves adipokine profiles, the effects of exercise intensity when matched for energy expenditure on adiposopathy are unknown. We hypothesized that high-intensity exercise would elicit greater changes in adiposopathy compared to moderate exercise. Twenty-eight overweight and obese adults (age: 60.9±8.4years; BMI: 33.0±5.4kgm-2 ) with prediabetes were randomized to twelve 60-min sessions of either moderate-continuous (CONT; n=14) or high-intensity interval (INT; n=14) exercise training. Total and high molecular weight (HMW) adiponectin and leptin were collected to assess adiposopathy (ratio of total adiponectin to leptin; A/L). Insulin sensitivity (SIIS ) was determined using a 75goral glucose tolerance test before and after training. Cardiometabolic risk factors were measured and a z-score was calculated to determine metabolic syndrome (MetS) severity. CONT and INT increased A/L (P<0.01) and decreased leptin (P<0.01) and MetS severity (P=0.04). Neither intervention altered circulating levels of HMW adiponectin (P=0.76) and only INT increased total adiponectin levels (P=0.02). Both intensities increased insulin sensitivity (P<0.01), which was associated with improvements in A/L (r=0.47, P=0.01). Additionally, increases in A/L tended to relate to decreased MetS severity (r=-0.36, P=0.09). Short-term exercise intensity, when matched for energy expenditure, does not differentially affect improvements in adiposopathy in overweight and obese adults with prediabetes. Further, 12 bouts of exercise improved insulin sensitivity and MetS severity, suggesting that improving adipokine profiles may aid in reducing cardiometabolic risk.

Chronic aerobic exercise improves insulin sensitivity and modulates Nrf2 and NF‑κB/IκBα pathways in the skeletal muscle of rats fed with a high fat diet.

The present study aimed to investigate the molecular mechanisms of the ameliorative effects of chronic aerobic exercise on non-alcoholic steatohepatitis (NASH) in rat skeletal muscle. Female Sprague-Dawley rats (n=6–9 per group) were divided into four groups: i) Rats fed with normal chow; ii) exercise rats fed with normal chow + exercise (run on a rotarod for 30 min per day from 9–12 weeks); iii) rats fed with a high-fat diet (HFD); iv) rats fed with an HFD + exercise. All HFD rats were fed with an HFD consisting of 30% fat from fish oil throughout the study for 12 weeks. Exercise decreased the levels of hepatic lipogenic markers carbohydrate-responsive element-binding protein, fat-specific protein 27 and liver X receptor and improved systemic glucose and insulin intolerance in the NASH animal model. The beneficial effects may have been mediated partly via the tripartite motif-containing family protein 72 (TRIM72)/PI3K/Akt/mTOR pathway, accompanied with an upregulation of glucose transporter 4 in the skeletal muscle. The exercise regimen activated the master regulator of antioxidant enzymes, nuclear factor erythroid 2-related factor 2, with upregulation of superoxide dismutase [Cu-Zn] expression and a corresponding decrease in kelch-like ECH-associated protein 1 expression, but failed to decrease the levels of the oxidative marker malondialdehyde in the HFD rat skeletal muscle. Chronic exercise decreased the expression of the inflammation marker NF-κB, followed by a decrease in interleukin-6 and tumor necrosis factor-α levels, as verified by a corresponding increase in the level of NF-κB inhibitor α expression. Exercise may exert its beneficial effects by improving muscle insulin sensitivity via the TRIM72/PI3K/Akt/mTOR pathway, contributing to the improvement of systemic insulin intolerance, and finally leading to decreased hepatic lipogenesis during NASH. The attenuation of insulin resistance by exercise may be partly achieved through a decrease in the level of inflammation and an increased antioxidant response.

Effect of essential amino acid supplementation and aerobic exercise on insulin sensitivity in healthy older adults: A randomized clinical trial

The combination of prolonged essential amino acid (EAA) supplementation and aerobic exercise training (Ex) improves muscle protein metabolism, strength and function in healthy older adults. However, excess EAA intake may worsen insulin sensitivity. Here we report the effects of EAA supplementation (EAA, n=11), placebo (PLA, n=10), aerobic exercise with placebo (Ex+PLA, n=11) or Ex with EAA supplementation (Ex+EAA, n=10) for 22 weeks on insulin sensitivity in non-diabetic older adults. A 2×2 design with block randomization and double blinding for supplement or placebo was used. Subjects ingested EAA (15g) or placebo daily. Exercising subjects participated in supervised progressive vigorous treadmill walking 3 times weekly. Measures of insulin sensitivity by oral glucose tolerance testing were collected at baseline and 22 weeks. Dietary intakes of protein and specific amino acids were determined in a subset of subjects. Overall, exercise improved insulin sensitivity, while EAA supplementation had no effect. In the dietary subset, post-intervention insulin sensitivity did not correlate significantly with the total intake of EAA, anti-angiogenic amino acids (cysteine, methionine), or branched-chain amino acids (isoleucine, leucine, valine). Overall, we conclude that in healthy older adults with moderate protein intake, EAA supplementation is metabolically safe as it does not decrease insulin sensitivity regardless of its combination with aerobic exercise. Thus, daily protein intake should be controlled for when modeling insulin sensitivity. Future studies should explore the role of increased blood flow as a potential explanatory factor for the observed interaction between aerobic exercise and supplementation. NCT00872911.

Adeno-Associated Virus-Mediated Knockdown of SLC16A11 Improves Glucose Tolerance and Hepatic Insulin Signaling in High Fat Diet-Fed Mice.

SLC16A11, a member of the SLC16 family, is associated with lipid metabolism, causing increased intracellular triacylglycerol (TAG) levels. In the current study, our primary goal was to determine if an SLC16A11 knockdown would improve glucose tolerance and hepatic insulin signaling in high fat diet (HFD)-fed mice. Additionally, the mechanism for exercise-improved insulin sensitivity remains unclear, and there is no mechanistic insight into SLC16A11's role in insulin sensitivity under exercise stress. Therefore, we also examined the impact of endurance exercise on the abundance of SLC16A11. C57BL/6 J male mice were fed either regular chow (Control) or HFD for 8 weeks and then injected with adeno-associated virus (AAV). Plasma parameters, tissue lipid contents, glucose tolerance, and expression profiles of hepatic insulin signaling were detected. Also, other mice were divided randomly into sedentary and exercise groups. We assessed hepatic expression of SLC16A11 after 8 weeks of endurance exercise. 1) Hepatic SLC16A11 expression was greater in HFD-fed mice compared to Control mice. 2) AAV-mediated knockdown of SLC16A11 improved glucose tolerance, prevented TAG accumulation in serum and liver, and increased phosphorylation of protein kinase B (Akt) and glycogen synthesis kinase-3β (GSK3β) in HFD-fed mice. 3) Endurance exercise decreased hepatic SLC16A11 expression. Inactivation of SLC16A11, which is robustly induced by HFD, improved glucose tolerance and hepatic insulin signaling, independent of body weight, but related to TAG. Additionally, SLC16A11 might mediate the health benefits of endurance exercise.

291-OR: Exercise Modulates Glucose Metabolism in Part through Changes in the Gut Microbiome

Exercise is one of the most prescribed interventions in the treatment/prevention of diabetes and metabolic disease. It is well established that different diets affect the distribution of gut microbiota. It has recently been shown that exercise may also modify the gut microbome and these modifications may differ depending on the obesity status of the individual. In this work we investigated whether metabolic changes triggered by exercise are transferable via cecum microbiota transplantationand how this would impact on the obesity response to high fat diet (HFD). Ten-week old, B6J male mice, on chow diet, were reared under either standard sedentary conditions or with access to a running wheel for 4 weeks. Under these conditions the latter mice ran an average of 6 Km per day. Mice were scarified, fecal DNA were sequenced and the cecum microbiota were transplanted into germ-free mice in the presence/absence of HFD. As expected, exercise improved insulin sensitivity and glucose tolerance in the donor mice. Shotgun metagenomic analysis of gut microbiota revealed that exercise was associated with decreased relative abundance of Parasutterella_excrementihominis and Bacteroides_thetaiotaomicron and increased Clostridium clostridioforme CAG:511 and Lactobacillus murinus ASF361. Functional composition of the bacterial metagenome indicated these changes resulted in an upregulation of microbial pathways of valine and methionine metabolism. More importantly, transplant of cecum microbiota from exercised donors to non-exercise donors improved running capacity in lean mice and improved glucose tolerance in mice on HFD. In both groups, this was associated with increased glucose uptake in skeletal muscle soleus and BAT. In summary, exercise reshapes the gut microbiome to improve whole body glucose metabolism, and this effect can be transferred by microbiome transplant. This provides an new opportunity in the treatment of obesity-related insulin resistance. Disclosure B. Brandao: None. M.E. Li: None. W. Cai: None. T.M. Batista: None. M.F. Hirshman: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen Inc., Colgate-Palmolive Company, Medtronic. L.J. Goodyear: None. C. Kahn: Advisory Panel; Self; MedImmune. Board Member; Self; Kaleido Biosciences. Consultant; Self; AntriaBio, Inc., Cobalt Therapeutics, Flagship Pioneering. Research Support; Self; Alnylam. Funding National Institute of Diabetes and Digestive and Kidney Diseases

Exercise Induction of Key Transcriptional Regulators of Metabolic Adaptation in Muscle Is Preserved in Type 2 Diabetes.

Type 2 diabetes (T2D) is characterized by insulin resistance in skeletal muscle. Regular exercise improves insulin sensitivity, mitochondrial function, and energy metabolism. Thus, an impaired response to exercise may contribute to insulin resistance. We hypothesized that key transcriptional regulators of metabolic adaptation to exercise show an attenuated response in skeletal muscle in T2D. Skeletal muscle biopsies were obtained from 13 patients with T2D and 14 age- and weight-matched controls before, immediately after 1 hour acute exercise (70% maximal pulmonary oxygen uptake), and 3 hours into recovery to examine mRNA expression of key transcription factors and downstream targets and activity of key upstream kinases underlying the metabolic adaptation to exercise. Acute exercise increased gene expression of the nuclear hormone receptor 4A (NR4A) subfamily (∼4- to 36-fold) and other key transcription factors, including ATF3, EGR1, JUNB, SIK1, PPARA, and PPARG (∼1.5- to 12-fold), but with no differences between groups. The expression of NR4A1 (approximately eightfold) and NR4A3 (∼75-fold) was further increased 3 hours into recovery, whereas most muscle transcripts sustained elevated or returned to basal levels, again with no differences between groups. Muscle expression of HKII and SLC2A4 and hexokinase II protein content were reduced in patients with T2D. The phosphorylation of p38 MAPK, Erk1/2, Ca2+/calmodulin-dependent kinase II, and cAMP-responsive element-binding protein was equally increased in response to exercise and/or recovery in both groups. Acute exercise elicits a pronounced and overall similar increase in expression of key transcription factors and activation of key upstream kinases involved in muscle metabolic adaptation to exercise in patients with T2D and weight-matched controls.

Effects of exercise and dietary protein sources on adiposity and insulin sensitivity in obese mice

Low-fat diets and exercise are generally assumed to ameliorate obesity-related metabolic dysfunctions, but the importance of exercise vs. dietary changes is debated. Male C57BL/6J mice were fed a high-fat/high-sucrose (HF/HS) diet to induce obesity and then either maintained on the HF/HS or shifted to low-fat (LF) diets containing either salmon or entrecote. For each diet, half of the animals exercised voluntarily for 8 weeks. We determined body composition, glucose tolerance, insulin sensitivity and hepatic triacylglycerol levels. The microbiota composition in cecal and fecal samples was analyzed using 16S ribosomal RNA gene amplicon sequencing. Voluntary exercise improved insulin sensitivity but did not improve glucose tolerance. Voluntary exercise did not reduce adiposity in mice maintained on an HF/HS diet but enhanced LF-induced reduction in adiposity. Hepatic triacylglycerol levels were reduced by voluntary exercise in LF- but not HF/HS-fed mice. Voluntary exercise induced shifts in the cecal and fecal microbiota composition and functional potential in mice fed LF or HF/HS diets. Whereas voluntary exercise improved insulin sensitivity, a switch to an LF diet was the most important factor related to body weight and fat mass reduction.

Post-Exercise Carbohydrate-Energy Replacement Attenuates Insulin Sensitivity and Glucose Tolerance the Following Morning in Healthy Adults.

The carbohydrate deficit induced by exercise is thought to play a key role in increased post-exercise insulin action. However, the effects of replacing carbohydrate utilized during exercise on postprandial glycaemia and insulin sensitivity are yet to be determined. This study therefore isolated the extent to which the insulin-sensitizing effects of exercise are dependent on the carbohydrate deficit induced by exercise, relative to other exercise-mediated mechanisms. Fourteen healthy adults performed a 90-min run at 70% max starting at 1600–1700 h before ingesting either a non-caloric artificially-sweetened placebo solution (CHO-DEFICIT) or a 15% carbohydrate solution (CHO-REPLACE; 221.4 ± 59.3 g maltodextrin) to precisely replace the measured quantity of carbohydrate oxidized during exercise. The alternate treatment was then applied one week later in a randomized, placebo-controlled, and double-blinded crossover design. A standardized low-carbohydrate evening meal was consumed in both trials before overnight recovery ahead of a two-hour oral glucose tolerance test (OGTT) the following morning to assess glycemic and insulinemic responses to feeding. Compared to the CHO-DEFICIT condition, CHO-REPLACE increased the incremental area under the plasma glucose curve by a mean difference of 68 mmol·L−1 (95% CI: 4 to 132 mmol·L−1; p = 0.040) and decreased the Matsuda insulin sensitivity index by a mean difference of −2 au (95% CI: −1 to −3 au; p = 0.001). This is the first study to demonstrate that post-exercise feeding to replaceme the carbohydrate expended during exercise can attenuate glucose tolerance and insulin sensitivity the following morning. The mechanism through which exercise improves insulin sensitivity is therefore (at least in part) dependent on carbohydrate availability and so the day-to-day metabolic health benefits of exercise might be best attained by maintaining a carbohydrate deficit overnight.

Exercise Improves Insulin Sensitivity in the Absence of Changes in Cytokines.

The benefits of aerobic exercise training on insulin sensitivity in subjects with metabolic syndrome (MetS) are, at least in part, associated with changes in cytokines. Recent studies identified novel cytokines (e.g., fractalkine, omentin, and osteopontin) that are strongly involved in glucose homeostasis and therefore potentially contribute in the exercise-induced changes in insulin sensitivity. Therefore, we aim to examine changes in skeletal muscle RNA expression and plasma levels of novel cytokines after exercise training and correlate these changes to the exercise-induced changes in insulin sensitivity. Women with metabolic syndrome (MetS, n = 11) and healthy women (n = 10) participated in a 6-month aerobic exercise training intervention (three times a week, 45 min per session at 65%-85% of individual heart rate reserve). Before and after training, we examined insulin sensitivity (M value during hyperinsulinemic euglycemic clamp) and circulating blood levels of cytokines (venous blood sample; leptin, adiponectin, omentin, fraktalkin, and osteopontin). The skeletal muscle RNA expression of these cytokines (muscle biopsy) was examined in two subgroups (MetS, n = 6; healthy women, n = 6). At baseline, plasma levels of omentin (85.8 ± 26.2 ng·mL) and adiponectin (5.0 ± 1.7 μg·mL) levels were significantly higher in controls compared with MetS (51.1 ± 27.1; 3.6 ± 1.1 respectively), and leptin levels were lower in controls (18.7 ± 11.5 vs 53.0 ± 23.5 ng·mL). M value was significantly higher in controls (8.1 ± 1.9 mg·kg·min) than in MetS (4.0 ± 1.7). Exercise training significantly improved M values in both groups (P < 0.01). Exercise training did not alter plasma and skeletal muscle RNA expression levels of cytokines, but no correlation was observed between changes in cytokine level/RNA expression and M values (P > 0.05). Although exercise training successfully improves insulin sensitivity in MetS and healthy women, we found no change in plasma and mRNA expression levels of novel cytokines.

The Effect of Vigorous- Versus Moderate-Intensity Aerobic Exercise on Insulin Action.

Due to the beneficial effects on a wide range of modern medical conditions, most professional societies recommend regular aerobic exercise as part of a healthy lifestyle. Many of the exercise-related health benefits exhibit a dose-response relationship: Up to a point, more exercise is more beneficial. However, recent studies have suggested that different exercise intensities may provide distinct health benefits, independent of energy expenditure (i.e., exercise dose). One of these benefits, primarily mediated by the skeletal muscle, is exercise-related changes in insulin action and glucose homeostasis. Glucose uptake in the exercising muscle occurs through insulin-independent mechanisms whose downstream signaling events ultimately converge with insulin-signaling pathways, a fact that may explain why exercise and insulin have additive effect on skeletal muscle glucose uptake. Although the existing evidence is somewhat conflicting, well-controlled randomized studies suggest that, when controlled for total energy expenditure, moderate-intensity aerobic exercise improves insulin sensitivity more than vigorous-intensity aerobic exercise. The mechanisms underlying this difference are largely unknown. One possible explanation involves enhanced metabolism of fatty acid stores in the skeletal muscle by moderate-intensity exercise, which may directly improve insulin sensitivity. Overall, new technologic and physiologic investigative tools are beginning to shed light on the biology. Further understanding of these mechanisms will lead to better understanding of the clinical implications of a healthy lifestyle and may ultimately offer new therapeutic targets for common medical conditions such as insulin resistance and diabetes.

Weight supported quadrupedal treadmill exercise improves insulin sensitivity in a rat model of spinal cord injury and diabetes

Previous studies have shown exercise is a simple and economical therapeutic modality that effectively benefits patients with type 2 diabetes. Spinal cord injured (SCI) individuals have a high risk for developing type 2 diabetes. However, there have been no studies that have examined the effects of treadmill exercise in individuals with SCI and type 2 diabetes. We examined the effects of imposing quadrupedal body weight supported treadmill exercise in a rodent model of SCI and type 2 diabetes. Seventeen rats received a severe spinal cord contusion (T10). One day after the contusion, the rats were placed on a high energy diet (10% fat, 20% sucrose, and 70% rodent chow) and 40 days later, a low dose of streptozotocin (STZ; 30 mg/kg, i.p.) was administered. The rats were assigned to an exercise (n=8) or non‐exercise group (n=9). Exercise consisted of weight supported, quadrupedal treadmill walking (23 cm/s) for 1 hr/day, 5 days/week for 6 weeks. Insulin tolerance tests were performed, hemodynamic measurements were recorded, and heart and hindlimb muscle tissue was harvested after the rats were killed. Based on fasting blood glucose, the high energy diet and STZ treatment was successful in inducing diabetes in the rats (i.e. &gt;140 mg/dL; exercise: 202±50 mg/dL; non‐exercise: 146±29 mg/dL). Fasting blood glucose levels were not significantly different between the groups. However, insulin sensitivity was improved by exercise based on insulin tolerance test. We found significant differences in glucose levels 45 and 60 min after insulin injection indicating a greater insulin sensitivity in the exercised group. Exercise also significantly increased tibialis anterior, gastrocnemius and soleus muscle weights by 7%, 20%, 31% respectively indicating the exercise was effective in activating hindlimb activity in the SCI rats. These findings suggest for the first time that weight supported treadmill exercise can reduce metabolic abnormalities that occur after SCI.Support or Funding InformationNIH grant R15NS082711 to R. de Leon

Proteomics of Skeletal Muscle: Focus on Insulin Resistance and Exercise Biology.

Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence, of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle proteomics are challenging. This review describes the technical limitations of skeletal muscle proteomics as well as emerging developments in proteomics workflow with respect to samples preparation, liquid chromatography (LC), MS and computational analysis. These technologies have not yet been fully exploited in the field of skeletal muscle proteomics. Future studies that involve state-of-the-art proteomics technology will broaden our understanding of exercise-induced adaptations as well as molecular pathogenesis of insulin resistance. This could lead to the identification of new therapeutic targets.

Combination of bofutsushosan (Kampo medicine) and voluntary exercise improves insulin sensitivity in Otsuka Long-Evans Tokushima fatty rats

Aim Previous studies have shown that the traditional Kampo medicine bofutsushosan (BTS) has an anti-obesity effect. In the current study, we investigated the effects of BTS and voluntary exercise, and their combination on insulin sensitivity in Otsuka Long-Evans Tokushima fatty (OLETF) rats. Methods Male OLETF rats aged 16 weeks were divided into four groups: standard powdered diet (C); powdered diet containing BTS (BTS); access to a running wheel for voluntary running exercise and standard diet (EX); and combined BTS and EX (BTS + EX). After 7 weeks, euglycemic clamp (insulin infusion rate: 3.0 mU/kg/min) was performed in awake rats and the insulin-signaling pathway in skeletal muscle was evaluated. Results At 23 weeks of age, C, BTS, EX and BTS + EX rats showed an average of 656, 582, 459 and 417 g and had epididymal fat mass of 2.99, 2.36, 1.09 and 0.66 g/100 g bodyweight respectively. Glucose infusion rate (GIR) during euglycemic clamp was significantly higher in BTS and EX rats than in C rats. In addition, GIR in BTS + EX rats was significantly higher than in C, BTS and EX rats. The total content of skeletal muscle insulin receptor β-subunit and insulin receptor substrate-1 protein was significantly increased in EX and BTS + EX rats compared with C rats. Conclusion Combination of BTS and EX could be considered beneficial for the prevention and treatment of obesity-induced type 2 diabetes mellitus.

Diet-induced increases in chemerin are attenuated by exercise and mediate the effect of diet on insulin and HOMA-IR.

Chemerin concentrations are elevated in obesity and associated with inflammation and insulin resistance. Exercise improves insulin sensitivity, which may be facilitated by changes in chemerin. We explored the effects of chronic exercise on chemerin levels in diet-induced obese mice. We divided 40 mice into 4 groups: high-fat diet/exercise, high-fat diet/sedentary, normal diet/exercise, and normal diet/sedentary. A 9-week dietary intervention was followed by a 12-week exercise intervention (treadmill run: 11 m/min for 30 min, 3×/week). We analyzed blood samples before and after the exercise intervention. We used t-tests and linear regression to examine changes in chemerin, insulin resistance, and inflammatory markers, and associations between changes in chemerin and all other biomarkers. Chemerin increased significantly across all mice over the 12-week intervention (mean ± SD = 40.7 ± 77.8%, p = 0.01), and this increase was smaller in the exercise versus sedentary mice (27.2 ± 83.9% versus 54.9 ± 70.5%, p = 0.29). The increase among the high-fat diet/exercise mice was ~44% lower than the increase among the high-fat diet/sedentary mice (55.7 ± 54.9% versus 99.8 ± 57.7%, p = 0.12). The high-fat diet mice showed significant increases in insulin (773.5 ± 1286.6%, p < 0.0001) and homeostatic model assessment of insulin resistance (HOMA-IR; 846.5 ± 1723.3%, p < 0.01). Mediation analyses showed that increases in chemerin explained a substantial amount of the diet-induced increases in insulin and HOMA-IR. Chronic exercise may attenuate diet-driven increases in circulating chemerin, and the insulin resistance associated with a high-fat diet may be mediated by diet-induced increases in chemerin.