The Lipid Peroxidation End-Product 4-Hydroxynonenal Induces Insulin Resistance in Isolated Rat Slow-Twitch Skeletal Muscle

A primary defect leading to the development of type 2 diabetes is insulin resistance of the glucose transport system in skeletal muscle. One factor known to induce insulin resistance is oxidative stress. A by>product of lipid peroxidation is the reactive aldehyde 4-hydroxynonenal (4-HNE), an oxidant that induces a number of deleterious consequences on cell function. However, the impact of 4-HNE on the glucose transport system in rat slow>twitch skeletal muscle is currently not known. Therefore, we assessed the impact of 4-HNE on insulin signaling factors (IRS-1 protein expression and phosphorylation of Akt Ser473 (pAkt) and AS160 Thr642 (pAS160)) and on glucose transport activity in mammalian slow-twitch muscle. Strips of soleus muscle from lean Zucker rats were incubated with 4-HNE (50 μM) in the absence or presence of insulin (5 mU/ml) for up to 6 hr. Insulin>stimulated glucose transport activity (determined using 2-deoxyglucose uptake) was decreased by 4-HNE at 2 hr (30%), 4 hr (26%), and 6 hr (39%) (all pproduct and oxidant 4-HNE induces insulin resistance of glucose transport activity in rat slow>twitch skeletal muscle, initially associated with impaired phosphorylation (and therefore reduced activation) of AS160. Longer durations of 4-HNE exposure led to a greater impairment of Akt phosphorylation and to a selective loss of IRS-1 protein. These results provide further support for an important role of oxidative stress in the etiology of skeletal muscle insulin resistance

The Serine Kinase C-Jun N-Terminal Kinase (JNK) Contributes to Oxidant-Induced Insulin Resistance in Isolated Rat Skeletal Muscle

Insulin resistance of the mammalian skeletal muscle glucose transport system, one cause of which is oxidative stress, leads to the development of type 2 diabetes. While the direct contributions to insulin resistance of certain stress-activated serine kinases have been described previously, the specific contribution of c-Jun N-terminal kinase (JNK) is not fully understood. Therefore, we assessed the role of JNK in insulin resistance caused by in vitro exposure to the oxidant hydrogen peroxide (H₂O₂). Soleus muscles from lean Zucker rats were incubated in low levels (~30 μM) of H₂O₂ in the absence or presence of insulin for up to 6 hr. Decreases in insulin-stimulated glucose transport activity (ISGTA) were observed at all time points and were associated with similar diminutions in insulin stimulation of Akt Ser⁴⁶⁷ phosphorylation. Phosphorylation (Thr¹⁸³/Tyr¹⁸⁵) of JNK isoforms (JNK1 and JNK2/3) was increased by H₂O₂ in the absence and presence of insulin at all time points. To determine the specific contribution of JNK to oxidant-induced insulin resistance, the JNK inhibitor SP600125 was used. ISGTA in the presence of H₂O₂ was improved when the inhibitor was added during the 6-hr incubation. These results indicate that JNK contributes to oxidative stress-induced insulin resistance in mammalian skeletal muscle

The Serine Kinase C-Jun N-Terminal Kinase (JNK) Contributes to Oxidant-Induced Insulin Resistance in Isolated Rat Skeletal Muscle

Insulin resistance of the mammalian skeletal muscle glucose transport system, one cause of which is oxidative stress, leads to the development of type 2 diabetes. While the direct contributions to insulin resistance of certain stress-activated serine kinases have been described previously, the specific contribution of c-Jun N-terminal kinase (JNK) is not fully understood. Therefore, we assessed the role of JNK in insulin resistance caused by in vitro exposure to the oxidant hydrogen peroxide (H₂O₂). Soleus muscles from lean Zucker rats were incubated in low levels (~30 μM) of H₂O₂ in the absence or presence of insulin for up to 6 hr. Decreases in insulin-stimulated glucose transport activity (ISGTA) were observed at all time points and were associated with similar diminutions in insulin stimulation of Akt Ser⁴⁶⁷ phosphorylation. Phosphorylation (Thr¹⁸³/Tyr¹⁸⁵) of JNK isoforms (JNK1 and JNK2/3) was increased by H₂O₂ in the absence and presence of insulin at all time points. To determine the specific contribution of JNK to oxidant-induced insulin resistance, the JNK inhibitor SP600125 was used. ISGTA in the presence of H₂O₂ was improved when the inhibitor was added during the 6-hr incubation. These results indicate that JNK contributes to oxidative stress-induced insulin resistance in mammalian skeletal muscle

DataSheet2_Effects of physical activity on the severity of illness and mortality in COVID-19 patients: A systematic review and meta-analysis.PDF

Purpose: This systematic review and meta-analysis investigated the association between Physical activity (PA) before Coronavirus Disease 2019 (COVID-19) infection and the severity of illness and mortality in COVID-19 patients.Methods: A comprehensive search was undertaken to identify retrospective and nonrandomized controlled trial studies comparing the severity and mortality of COVID-19 infection among COVID-19 patients who had previously reported their participation in PA with those who had not. The databases searched were PubMed, Cochrane Library, Scopus, Science Direct, EMBASE, OPENGREY.EU, and ClinicalTrials.gov. The risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects model was used for determining pairwise meta-analyses. The protocol was registered with PROSPERO (CRD42021262548).Results: Eighteen studies met the inclusion criteria (5 cross-sectional, 12 cohort, and 1 case-control studies). All 1 618 680 subjects were adults. PA significantly decreased the risk of death in COVID-19 patients (odds ratio [OR] 0.34; 95% confidence interval [CI], 0.19–0.62; p Conclusion: PA before infection might reduce severity and mortality in COVID-19 patients, especially PA ≥ 150 min/wk of moderate activity or ≥75 min/wk of vigorous activity. However, careful interpretations should be considered due to the difference in PA patterns and severity definitions among included studies. This finding implies that engaging in regular PA, even in different patterns, has beneficial effects on the severity and mortality of COVID-19 patients.</p

DataSheet1_Effects of physical activity on the severity of illness and mortality in COVID-19 patients: A systematic review and meta-analysis.PDF

Purpose: This systematic review and meta-analysis investigated the association between Physical activity (PA) before Coronavirus Disease 2019 (COVID-19) infection and the severity of illness and mortality in COVID-19 patients.Methods: A comprehensive search was undertaken to identify retrospective and nonrandomized controlled trial studies comparing the severity and mortality of COVID-19 infection among COVID-19 patients who had previously reported their participation in PA with those who had not. The databases searched were PubMed, Cochrane Library, Scopus, Science Direct, EMBASE, OPENGREY.EU, and ClinicalTrials.gov. The risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects model was used for determining pairwise meta-analyses. The protocol was registered with PROSPERO (CRD42021262548).Results: Eighteen studies met the inclusion criteria (5 cross-sectional, 12 cohort, and 1 case-control studies). All 1 618 680 subjects were adults. PA significantly decreased the risk of death in COVID-19 patients (odds ratio [OR] 0.34; 95% confidence interval [CI], 0.19–0.62; p Conclusion: PA before infection might reduce severity and mortality in COVID-19 patients, especially PA ≥ 150 min/wk of moderate activity or ≥75 min/wk of vigorous activity. However, careful interpretations should be considered due to the difference in PA patterns and severity definitions among included studies. This finding implies that engaging in regular PA, even in different patterns, has beneficial effects on the severity and mortality of COVID-19 patients.</p