The growing interest in skeletal muscle regeneration is associated with the opening of new therapeutic strategies for muscle injury after trauma, as well as several muscular degenerative pathologies, including dystrop...The growing interest in skeletal muscle regeneration is associated with the opening of new therapeutic strategies for muscle injury after trauma, as well as several muscular degenerative pathologies, including dystrophies, muscu- lar atrophy, and cachexia. Studies focused on the ability of extracellular factors to promote myogenesis are therefore highly promising. We now report that an adipocyte-derived factor, globular adiponectin （gAd）, is able to induce mus- cle gene expression and cell differentiation, gAd, besides its well-known ability to regulate several metabolic func- tions in muscle, including glucose uptake and consumption and fatty acid catabolism, is able to block cell cycle entry of myoblasts, to induce the expression of specific skeletal muscle markers such as myosin heavy chain or caveolin-3, as well as to provoke cell fusion into multinucleated syncytia and, finally, muscle fibre formation, gAd exerts its pro- differentiative activity through redox-dependent activation of p38, Akt and 5＇-AMP-activated protein kinase path- ways. Interestingly, differentiating myoblasts are autocrine for adiponectin, and the mimicking of pro-inflammatory settings or exposure to oxidative stress strongly increases the production of the hormone from differentiating cells. These data suggest a novel function of adiponectin, directly coordinating the myogenic differentiation program and serving an autocrine function during skeletal myogenesis.展开更多
Background Endothelial dysfunction is a key event in the onset and progression of atherosclerosis in diabetic patients. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. However, ...Background Endothelial dysfunction is a key event in the onset and progression of atherosclerosis in diabetic patients. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. However, no study has addressed apoptosis in human umbilical vein endothelial cells （HUVECs） induced by an intermittent high-glucose media and its association with adiponectin receptor 1 （adipoR1）, adipoR2, or adenosine monophosphate （AMP）-activated protein kinase （AMPK）. Methods HUVECs were cultured in continuous normal glucose （5.5 mmol/L）, continuous high glucose （25 mmol/L）, alternating normal and high glucose and mannitol. In the alternating normal and high-glucose media, HUVECs were treated under different conditions. First, cells were transfected with the adipoRl-specific small-interfering RNA （siRNA） and then stimulated with globular adiponectin （gAD）. Second, cells were cultured in both gAD and the AMPK activator 5-aminoimidazole-4-carboxamide-l-13-D-ribofuranoside （AICAR）. Third, cells were cultured in the AMPK inhibitor adenine-9-13-D-arabino-furanoside （araA）, gAD, and in AICAR. Results HUVEC apoptosis increased more significantly in an intermittent high-glucose medium than in a constant high-glucose medium. HUVEC apoptosis induced by an intermittent high-glucose medium was inhibited when the cells were pretreated with 3 pg/ml gAD, which rapidly activated AMPK and adipoR1 in HUVECs. However, adipoR2 was not activated. Conclusions We found that adipoR1, not adipoR2, is involved in mediating intermittent high-concentration glucose- evoked apoptosis in endothelial cells, gAD activated AMPK through adipoR1, leads to the partial inhibition of HUVEC apoptosis. A fluctuating glucose medium is more harmful than a constant high-glucose medium to endothelial cells.展开更多
文摘The growing interest in skeletal muscle regeneration is associated with the opening of new therapeutic strategies for muscle injury after trauma, as well as several muscular degenerative pathologies, including dystrophies, muscu- lar atrophy, and cachexia. Studies focused on the ability of extracellular factors to promote myogenesis are therefore highly promising. We now report that an adipocyte-derived factor, globular adiponectin （gAd）, is able to induce mus- cle gene expression and cell differentiation, gAd, besides its well-known ability to regulate several metabolic func- tions in muscle, including glucose uptake and consumption and fatty acid catabolism, is able to block cell cycle entry of myoblasts, to induce the expression of specific skeletal muscle markers such as myosin heavy chain or caveolin-3, as well as to provoke cell fusion into multinucleated syncytia and, finally, muscle fibre formation, gAd exerts its pro- differentiative activity through redox-dependent activation of p38, Akt and 5＇-AMP-activated protein kinase path- ways. Interestingly, differentiating myoblasts are autocrine for adiponectin, and the mimicking of pro-inflammatory settings or exposure to oxidative stress strongly increases the production of the hormone from differentiating cells. These data suggest a novel function of adiponectin, directly coordinating the myogenic differentiation program and serving an autocrine function during skeletal myogenesis.
文摘Background Endothelial dysfunction is a key event in the onset and progression of atherosclerosis in diabetic patients. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. However, no study has addressed apoptosis in human umbilical vein endothelial cells （HUVECs） induced by an intermittent high-glucose media and its association with adiponectin receptor 1 （adipoR1）, adipoR2, or adenosine monophosphate （AMP）-activated protein kinase （AMPK）. Methods HUVECs were cultured in continuous normal glucose （5.5 mmol/L）, continuous high glucose （25 mmol/L）, alternating normal and high glucose and mannitol. In the alternating normal and high-glucose media, HUVECs were treated under different conditions. First, cells were transfected with the adipoRl-specific small-interfering RNA （siRNA） and then stimulated with globular adiponectin （gAD）. Second, cells were cultured in both gAD and the AMPK activator 5-aminoimidazole-4-carboxamide-l-13-D-ribofuranoside （AICAR）. Third, cells were cultured in the AMPK inhibitor adenine-9-13-D-arabino-furanoside （araA）, gAD, and in AICAR. Results HUVEC apoptosis increased more significantly in an intermittent high-glucose medium than in a constant high-glucose medium. HUVEC apoptosis induced by an intermittent high-glucose medium was inhibited when the cells were pretreated with 3 pg/ml gAD, which rapidly activated AMPK and adipoR1 in HUVECs. However, adipoR2 was not activated. Conclusions We found that adipoR1, not adipoR2, is involved in mediating intermittent high-concentration glucose- evoked apoptosis in endothelial cells, gAD activated AMPK through adipoR1, leads to the partial inhibition of HUVEC apoptosis. A fluctuating glucose medium is more harmful than a constant high-glucose medium to endothelial cells.
