Impaired Muscle AMPK Activation in the Metabolic Syndrome May Attenuate Improved Insulin Action after Exercise Training

Layne, Andrew S.; Nasrallah, Sami N.; South, Mark A.; Howell, Mary E. A.; McCurry, Melanie P.; Ramsey, Michael W.; Stone, Michael H.; Stuart, Charles Alexander

doi:10.1210/jc.2010-2532

Cited by 38 publications

(65 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Together, these data suggest that the presence of IFG in adults with IGT modifies exercise training-induced improvements in glucose regulation. Although exercise generally increases insulin sensitivity in adults across the glucose continuum (11,22,26,35), the data are consistent with carefully controlled studies reporting that people with metabolic syndrome or early-onset type 2 diabetes have less improvement in clamp-derived whole body insulin sensitivity following 12 wk of exercise compared with healthy age, weight, and fitness-matched counterparts (25,30). In addition, the Diabetes Prevention Program Outcomes Study emphasized recently that adults with more severe forms of prediabetes were least likely to regress to normal glucose tolerance (37).…”

Section: Discussionsupporting

confidence: 76%

“…However, given that in vivo (29,42) and in vitro studies (3) report that chronic hyperglycemia overloads mitochondrial oxidative capacity, it appears plausible that exercising with a background of hyperglycemia impairs skeletal muscle glucose uptake through a metabolic stress/inflammatory-related pathway (36). This hypothesis is consistent with evidence that PGC-1␣ and AMPK expression are lower after exercise in insulin-resistant individuals (13,24,30).…”

Section: Discussionmentioning

confidence: 61%

See 1 more Smart Citation

Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes

Malin

Haus

Solomon

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Malin SK, Haus JM, Solomon TP, Blaszczak A, Kashyap SR, Kirwan JP. Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes. Am J Physiol Endocrinol Metab 305: E1292-E1298, 2013. First published September 24, 2013; doi:10.1152/ajpendo.00441.2013.-Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG ϩ IGT is unknown. Twenty-four older (66.7 Ϯ 0.8 yr) obese (34.2 Ϯ 0.9 kg/m 2 ) adults were categorized as IFG (n ϭ 8), IGT (n ϭ 8), or IFG ϩ IGT (n ϭ 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ϳ85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m 2 ·min Ϫ1 ) with [6,6-2 H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG ϩ IGT (P Ͻ 0.05). Exercise reduced glucose iAUCOGTT in IGT only (P Ͻ 0.05), and the decrease in glucose iAUCOGTT was inversely correlated with the increase in peripheral but not hepatic insulin sensitivity (P Ͻ 0.01). Increased clamp-derived peripheral insulin sensitivity was also correlated with enhanced metabolic flexibility, reduced fasting RQ, and higher nonoxidative glucose disposal (P Ͻ 0.05). Adults with IFG ϩ IGT had smaller gains in clamp-derived peripheral insulin sensitivity and metabolic flexibility, which was related to blunted improvements in postprandial glucose. Additional work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training. obesity; prediabetes; insulin resistance; cardiometabolic; exercise APPROXIMATELY 79 MILLION ADULTS in the US have impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG ϩ IGT) and are collectively referred to as having prediabetes (2). Focusing on adults with IFG, IGT, and IFG ϩ IGT is clinically important since each phenotype has a unique pathology that promotes different degrees of cardiovascular disease risk (8, 31). The exact cause for the difference in disease risk is unclear, but the degree of insulin resistance in skeletal muscle or the liver is a likely candidate. Individuals with IGT [2-h oral glucose tolerance test (OGTT) values between 140 and 199 mg/dl] are typically characterized as having reduced skeletal muscle insulin sensitivity, whereas adults with IFG (fasting glucose 100 -125 mg/dl) generally h...

show abstract

Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 61%

Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes

Malin

Haus

Solomon

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…This highlights the fact that the results of studies investigating the effects of exercise interventions on insulin sensitivity have been conflicting. Whereas some studies have reported greater benefits of exercise in people with poorer baseline insulin sensitivity (Jenkins & Hagberg, 2011), others have reported impaired responses to exercise in patients with T2D or metabolic syndrome (Layne et al, 2011;Sriwijitkamol et al, 2007), and longer T2D disease duration is associated with poorer improvements in insulin sensitivity and glycaemic control following aerobic exercise training (Solomon et al, 2013). In addition, it has been suggested that low response to exercise for important risk factors such as V O2max or insulin sensitivity may result in increased risk of developing cardiometabolic disease (Lessard et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, there are conflicting data on whether patients with T2D will have enhanced (Jenkins & Hagberg, 2011), or impaired (Layne et al, 2011;Sriwijitkamol et al, 2007) responses to exercise training in general, and therefore it remains unknown whether cyclingbased REHIT can be used to improve insulin sensitivity and V O2max in T2D patients, and whether it may be effective at improving other important health markers such as blood pressure, blood lipid profile, and body composition. Moreover, in order for any intervention to be recommended to patients with T2D, the effects of the intervention should be at least as good as those associated with current physical activity recommendations.…”

Section: Introductionmentioning

confidence: 99%

A comparison of the health benefits of reduced-exertion high-intensity interval training (REHIT) and moderate-intensity walking in type 2 diabetes patients

Ruffino

Songsorn

Haggett

et al. 2017

Appl. Physiol. Nutr. Metab.

View full text Add to dashboard Cite

show abstract

“…Recently, the authors found nondiabetic subjects with the metabolic syndrome had muscle fiber composition very similar to that seen in type 2 diabetes (9). This study was performed to determine whether the muscle fiber composition of metabolic syndrome subjects correlated with measures of insulin resistance.…”

mentioning

confidence: 94%

Slow-Twitch Fiber Proportion in Skeletal Muscle Correlates With Insulin Responsiveness

Stuart¹,

McCurry²,

Marino³

et al. 2013

The Journal of Clinical Endocrinology &Amp; Metabolism

Self Cite

186

146

View full text Add to dashboard Cite

Context:The metabolic syndrome, characterized by central obesity with dyslipidemia, hypertension, and hyperglycemia, identifies people at high risk for type 2 diabetes.Objective: Our objective was to determine how the insulin resistance of the metabolic syndrome is related to muscle fiber composition.Design: Thirty-nine sedentary men and women (including 22 with the metabolic syndrome) had insulin responsiveness quantified using euglycemic clamps and underwent biopsies of the vastus lateralis muscle. Expression of insulin receptors, insulin receptor substrate-1, glucose transporter 4, and ATP synthase were quantified with immunoblots and immunohistochemistry.Participants and Setting: Participants were nondiabetic, metabolic syndrome volunteers and sedentary control subjects studied at an outpatient clinic. Main Outcome Measures:Insulin responsiveness during an insulin clamp and the fiber composition of a muscle biopsy specimen were evaluated.Results: There were fewer type I fibers and more mixed (type IIa) fibers in metabolic syndrome subjects. Insulin responsiveness and maximal oxygen uptake correlated with the proportion of type I fibers. Insulin receptor, insulin receptor substrate-1, and glucose transporter 4 expression were not different in whole muscle but all were significantly less in the type I fibers of metabolic syndrome subjects when adjusted for fiber proportion and fiber size. Fat oxidation and muscle mitochondrial expression were not different in the metabolic syndrome subjects. Conclusion:Lower proportion of type I fibers in metabolic syndrome muscle correlated with the severity of insulin resistance. Even though whole muscle content was normal, key elements of insulin action were consistently less in type I muscle fibers, suggesting their distribution was important in mediating insulin effects. ) has more than doubled since 1980 (1). Because of obesity-related illness, the average life expectancy in the United States may soon decline for the first time (2). The metabolic syndrome is a precursor to the development of overt diabetes (3). Insulin resistance and hyperinsulinemia are key elements of the metabolic syndrome that is characterized by visceral obesity, hypertension, hyperlipidemia, hyperglycemia, coronary heart disease, and increased mortality (4). The severity of insulin re- Abbreviations: BMI, body mass index; GIR, glucose infusion rate; GLUT4, glucose transporter 4; IRS-1, insulin receptor substrate-1; SSGIR, steady-state glucose infusion rate; VO 2 max, maximal oxygen consumption.

show abstract

Impaired Muscle AMPK Activation in the Metabolic Syndrome May Attenuate Improved Insulin Action after Exercise Training

Cited by 38 publications

References 51 publications

Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes

Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes

A comparison of the health benefits of reduced-exertion high-intensity interval training (REHIT) and moderate-intensity walking in type 2 diabetes patients

Slow-Twitch Fiber Proportion in Skeletal Muscle Correlates With Insulin Responsiveness

Contact Info

Product

Resources

About