scholarly journals Adipocyte Differentiation-related Protein in Human Skeletal Muscle: Relationship to Insulin Sensitivity

2005 ◽  
Vol 13 (8) ◽  
pp. 1321-1329 ◽  
Author(s):  
Susan A. Phillips ◽  
Charles C. Choe ◽  
Theodore P. Ciaraldi ◽  
Andrew S. Greenberg ◽  
Alice P. S. Kong ◽  
...  
Diabetes ◽  
2000 ◽  
Vol 49 (5) ◽  
pp. 768-774 ◽  
Author(s):  
A. D. Baron ◽  
M. Tarshoby ◽  
G. Hook ◽  
E. N. Lazaridis ◽  
J. Cronin ◽  
...  

Diabetes ◽  
2017 ◽  
Vol 66 (6) ◽  
pp. 1501-1510 ◽  
Author(s):  
Kim A. Sjøberg ◽  
Christian Frøsig ◽  
Rasmus Kjøbsted ◽  
Lykke Sylow ◽  
Maximilian Kleinert ◽  
...  

2015 ◽  
Vol 309 (4) ◽  
pp. E388-E397 ◽  
Author(s):  
Adam J. Trewin ◽  
Leonidas S. Lundell ◽  
Ben D. Perry ◽  
Kim Vikhe Patil ◽  
Alexander V. Chibalin ◽  
...  

—Reactive oxygen species (ROS) produced in skeletal muscle may play a role in potentiating the beneficial responses to exercise; however, the effects of exercise-induced ROS on insulin action and protein signaling in humans has not been fully elucidated. Seven healthy, recreationally active participants volunteered for this double-blind, randomized, repeated-measures crossover study. Exercise was undertaken with infusion of saline (CON) or the antioxidant N-acetylcysteine (NAC) to attenuate ROS. Participants performed two 1-h cycling exercise sessions 7–14 days apart, 55 min at 65% V̇o2peak plus 5 min at 85%V̇o2peak, followed 3 h later by a 2-h hyperinsulinemic euglycemic clamp (40 mIU·min−1·m2) to determine insulin sensitivity. Four muscle biopsies were taken on each trial day, at baseline before NAC infusion (BASE), after exercise (EX), after 3-h recovery (REC), and post-insulin clamp (PI). Exercise, ROS, and insulin action on protein phosphorylation were evaluated with immunoblotting. NAC tended to decrease postexercise markers of the ROS/protein carbonylation ratio by −13.5% ( P = 0.08) and increase the GSH/GSSG ratio twofold vs. CON ( P < 0.05). Insulin sensitivity was reduced (−5.9%, P < 0.05) by NAC compared with CON without decreased phosphorylation of Akt or AS160. Whereas p-mTOR was not significantly decreased by NAC after EX or REC, phosphorylation of the downstream protein synthesis target kinase p70S6K was blunted by 48% at PI with NAC compared with CON ( P < 0.05). We conclude that NAC infusion attenuated muscle ROS and postexercise insulin sensitivity independent of Akt signaling. ROS also played a role in normal p70S6K phosphorylation in response to insulin stimulation in human skeletal muscle.


2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Aktham Mestareehi ◽  
Xiangmin Zhang ◽  
Berhane Seyoum ◽  
Zaher Msallaty ◽  
Abdullah Mallisho ◽  
...  

Context. Skeletal muscle insulin resistance is one of the primary contributors of type 2 diabetes (T2D). Metformin is the first-line drug for the treatment of T2D. The primary effects of metformin include decreasing glucose production in the liver and decreasing insulin resistance in the skeletal muscle. However, the molecular mechanism of metformin’s action in skeletal muscle is not well understood. Protein phosphatase 2A (PP2A), a major serine/threonine protein phosphatase, plays a pivotal role in cellular processes, such as signal transduction, cell proliferation, and apoptosis, and acts through dephosphorylating key signaling molecules such as AKT and AMPK. However, whether PP2A plays a role in metformin-induced insulin sensitivity improvement in human skeletal muscle cells remains to be elucidated. Objective. To investigate if PP2A plays a role in metformin-induced insulin sensitivity improvement in human skeletal muscle cells. Participants. Eight lean insulin-sensitive nondiabetic participants (4 females and 4 males; age: 21.0 ± 1.0 years; BMI: 22.0 ± 0.7   kg / m 2 ; 2-hour OGTT: 97.0 ± 6.0   mg / dl ; HbA1c: 5.3 ± 0.1 % ; fasting plasma glucose: 87.0 ± 2.0   mg / dl ; M value; 11.0 ± 1.0   mg / kgBW / min ). Design. A hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity in human subjects, and skeletal muscle biopsy samples were obtained. Primary human skeletal muscle cells (shown to retain metabolic characteristics of donors) were cultured from these muscle biopsies that included 8 lean insulin-sensitive participants. Cultured cells were expanded, differentiated into myotubes, and treated with 50 μM metformin for 24 hours before harvesting. PP2Ac activity was measured by a phosphatase activity assay kit (Millipore) according to the manufacturer’s protocol. Results. The results indicated that metformin significantly increased the activity of PP2A in the myotubes for all 8 lean insulin-sensitive nondiabetic participants, and the average fold increase is 1.54 ± 0.11 ( P < 0.001 ). Conclusions. These results provided the first evidence that metformin can activate PP2A in human skeletal muscle cells derived from lean healthy insulin-sensitive participants and may help to understand metformin’s action in skeletal muscle in humans.


2020 ◽  
Author(s):  
Hemang Parikh ◽  
Targ Elgzyri ◽  
Amra Alibegovic ◽  
Natalie Hiscock ◽  
Ola Ekström ◽  
...  

Abstract BackgroundInsulin resistance in skeletal muscle is a key feature of the pre-diabetic state, hypertension, dyslipidemia, cardiovascular diseases, and also predicts type 2 diabetes. However, the underlying molecular mechanisms are still poorly understood. MethodsTo explore these mechanisms, we related global skeletal muscle gene expression profiling of 38 non-diabetic men to physiological measures of insulin sensitivity. Results We identified 70 genes positively and 110 genes inversely correlated with insulin sensitivity in human skeletal muscle, identifying autophagy-related genes as positively correlated with insulin sensitivity. Replication in an independent study of 9 non-diabetic men resulted in 10 overlapping genes that strongly correlated with insulin sensitivity, including CPT1B and SIRT2 , involved in lipid metabolism, and FBXW5 that regulates mammalian target-of-rapamycin (mTOR) and autophagy. The expression of CPT1B , SIRT2 and FBXW5 was also positively correlated with the expression of key genes promoting the phenotype of an insulin sensitive myocyte e.g. PPARGC1A . ConclusionsThese data suggest that activation of genes involved in lipid metabolism, e.g. CPT1B and SIRT2 , and genes regulating autophagy and mTOR signaling, e.g. FBXW5 , are associated with increased insulin sensitivity in human skeletal muscle, reflecting a highly flexible nutrient sensing.


2013 ◽  
Vol 06 (05) ◽  
pp. 65-72 ◽  
Author(s):  
Andreas Vigelsø ◽  
Clara Prats ◽  
Thorkil Ploug ◽  
Flemming Dela ◽  
Jørn W. Helge

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