Effect of Acute Exercise on AMPK Signaling in Skeletal Muscle of Subjects With Type 2 Diabetes

Sriwijitkamol, Apiradee; Coletta, Dawn K.; Wajcberg, Estela; Balbontin, Gabriela B.; Reyna, Sara M.; Barrientes, John; Eagan, Phyllis A.; Jenkinson, Christopher P.; Cersósimo, Eugênio; DeFronzo, Ralph A.; Sakamoto, Kei; Musi, Nicolas

doi:10.2337/db06-1119

Cited by 285 publications

(278 citation statements)

References 63 publications

Supporting

Mentioning

230

Contrasting

Unclassified

Order By: Relevance

“…This observation suggests that the carriers of the minor alleles of T612M and 3U4898 have better control of glucose concentrations when in a hyperglycemic state, with concomitant reduction in DNA damage, leading to less inflammation (lower CRP) and thus lower prevalence of CVD. Exercise can increase expression of PPARGC1A in skeletal muscle of subjects with type 2 diabetes (14,50). We found that physical activity correlated with lower DNA damage.…”

Section: Discussionmentioning

confidence: 63%

PPARGC1A Variation Associated With DNA Damage, Diabetes, and Cardiovascular Diseases

et al. 2008

View full text Add to dashboard Cite

OBJECTIVE-Individuals with type 2 diabetes exhibit higher DNA damage and increased risk of cardiovascular disease (CVD). However, mechanisms underlying the association between DNA damage and development of type 2 diabetes and CVD are not understood. We sought to link peroxisome proliferatoractivated receptor-␥ coactivator-1 ␣ (PPARGC1A), a master transcriptional regulator of mitochondrial oxidative phosphorylation and cellular energy metabolism, with DNA damage, type 2 diabetes, and CVD.RESEARCH DESIGN AND METHODS-We measured DNA damage as urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration and examined the relationship between nine PPARGC1A genetic variants, DNA damage, type 2 diabetes, and self-reported CVD in 959 participants of the Boston Puerto Rican Health Study.RESULTS-With respect to urinary 8-OHdG, PPARGC1A variants showed significant association, and PPARGC1A haplotypes exhibited significant association after correction for multiple testing. Two independent PPARGC1A variants associated significantly with type 2 diabetes (odds ratios [ORs] 1.35 and 2.46; P ϭ 0.045 and Ͻ0.001). Carriers of minor alleles of two other PPARGC1A variants, both in strong linkage disequilibrium and associated with lower DNA damage, showed lower prevalence of CVD (ORs 0.53 and 0.65; P ϭ 0.030 and 0.175). Moreover, we found that physical activity correlated negatively with DNA damage.CONCLUSIONS-It is plausible that low physical activity combined with risk haplotyes contribute to the high prevalence of type 2 diabetes in this population. We propose that PPARGC1A influences development of type 2 diabetes and CVD via DNA damage. Increasing physical activity, which induces PPARGC1A expression, is a potential strategy to slow DNA damage, thereby decreasing the risk of CVD for individuals with type 2 diabetes.

show abstract

Section: Discussionmentioning

confidence: 63%

PPARGC1A Variation Associated With DNA Damage, Diabetes, and Cardiovascular Diseases

et al. 2008

View full text Add to dashboard Cite

show abstract

“…We and others (21,22) have shown that aerobic exercise has a dose-and intensity-related effect to increase insulin signaling and glucose transporter content in skeletal muscle. Exercise training increases insulin-stimulated glucose disposal and GLUT-4 (SLC2A4) protein content in obese patients with type 2 diabetes (22).…”

Section: Discussionmentioning

confidence: 85%

Physical Activity and Insulin Sensitivity

Balkau¹,

Mhamdi²,

Oppert³

et al. 2008

Diabetes

214

165

View full text Add to dashboard Cite

on behalf of the EGIR-RISC Study Group* OBJECTIVE-Physical activity is a modifiable risk factor for type 2 diabetes, partly through its action on insulin sensitivity. We report the relation between insulin sensitivity and physical activity measured by accelerometry.RESEARCH DESIGN AND METHODS-This is a cross-sectional study of 346 men and 455 women, aged 30 -60 years, without cardiovascular disease and not treated by drugs for diabetes, hypertension, dyslipidemia, or obesity. Participants were recruited in 18 clinical centers from 13 European countries. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Physical activity was recorded by accelerometry for a median of 6 days. We studied the relationship of insulin sensitivity with total activity (in counts per minute), percent of time spent sedentary, percent of time in light activity, and activity intensity (whether the participant recorded some vigorous or some moderate activity).RESULTS-In both men and women, total activity was associated with insulin sensitivity (P Ͻ 0.0001). Time spent sedentary, in light activity, and activity intensity was also associated with insulin sensitivity (P Ͻ 0.0004/0.01, 0.002/0.03, and 0.02/0.004, respectively, for men/women) but lost significance once adjusted for total activity. Adjustment for confounders such as adiposity attenuated the relationship with total activity; there were no interactions with confounders. Even in the 25% most sedentary individuals, total activity was significantly associated with better insulin sensitivity (P Ͻ 0.0001).CONCLUSIONS-Accumulated daily physical activity is a major determinant of insulin sensitivity. Time spent sedentary, time spent in light-activity, and bouts of moderate or vigorous activity did not impact insulin sensitivity independently of total activity.

show abstract

“…In skeletal muscle from lean type 2 diabetic patients [26,27] and obese participants [28], AMPK signalling in response to aminoimidazole carboxamide ribonucleotide (AICAR) or exercise appeared to be unchanged, although some studies have noticed modest reductions [29,30]. Thus, it is currently not clear whether a reduction in AMPK causes accumulation of skeletal muscle lipids and insulin resistance with obesity.…”

Section: Introductionmentioning

confidence: 99%

Reduced AMP-activated protein kinase activity in mouse skeletal muscle does not exacerbate the development of insulin resistance with obesity

et al. 2009

View full text Add to dashboard Cite

Aims/hypothesis Obesity-related insulin resistance is associated with accumulation of bioactive lipids in skeletal muscle. The AMP-activated protein kinase (AMPK) regulates lipid oxidation in muscle by inhibiting acetyl-CoA carboxylase-2 (ACC2) and increasing mitochondrial biogenesis. We investigated whether reduced levels of muscle AMPK promote lipid accumulation and insulin resistance during high-fat feeding. Methods Male C57/BL6 wild-type mice and transgenic littermates overexpressing an α2AMPK kinase-dead (KD) in muscle were fed control or high-fat diet. Whole-body glucose homeostasis was assessed by glucose and insulin tolerance tests, and by measuring fasting and fed serum insulin and glucose. Insulin action in muscle was determined by measuring 2-deoxy-[ 3 H]glucose uptake and Akt phosphorylation in incubated soleus and extensor digitorum longus muscles. Muscle triacylglycerol, diacylglycerol and ceramide content was measured by thin-layer chromatography. Mitochondrial proteins were measured by immunoblotting. Results KD mice had reduced skeletal muscle α2AMPK activity (50% in gastrocnemius and >80% in soleus and extensor digitorum longus) and ACC2 Ser228 phosphorylation (90% in gastrocnemius). High-fat feeding increased body mass and adiposity, and impaired insulin and glucose tolerance; however, there were no differences between wild-type and KD littermates. High-fat feeding impaired insulin-stimulated muscle glucose uptake and Akt-phosphorylation, while increasing muscle triacylglycerol, diacylglycerol (p=0.07) and ceramide, but these effects were not exacerbated in KD mice. In response to high-fat feeding, mitochondrial proteins were increased to similar levels in wild-type and KD muscles. Conclusions/interpretation Obesity-induced lipid accumulation and insulin resistance were not exacerbated in AMPK KD mice, suggesting that reduced levels of muscle α2AMPK do not promote insulin resistance in the early phase of obesity-related diabetes.

show abstract

Effect of Acute Exercise on AMPK Signaling in Skeletal Muscle of Subjects With Type 2 Diabetes

Cited by 285 publications

References 63 publications

PPARGC1A Variation Associated With DNA Damage, Diabetes, and Cardiovascular Diseases

PPARGC1A Variation Associated With DNA Damage, Diabetes, and Cardiovascular Diseases

Physical Activity and Insulin Sensitivity

Reduced AMP-activated protein kinase activity in mouse skeletal muscle does not exacerbate the development of insulin resistance with obesity

Contact Info

Product

Resources

About