The Use of Human Skeletal Muscle in Vitro for Biochemical and Pharmacological Studies of Glucose Uptake

1973 ◽  
Vol 44 (1) ◽  
pp. 55-62 ◽  
Author(s):  
K. N. Frayn ◽  
P. I. Adnitt ◽  
P. Turner
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Metabolic Control ◽  
Rat Heart ◽  
Human Skeletal Muscle ◽  
Antidiabetic Drug ◽  
Pharmacological Studies

1. A method is described for measuring glucose uptake by pieces of human skeletal muscle removed at surgery. 2. Glucose uptake by this preparation was stimulated by insulin (0.1–10 munits/ml) and inhibited by 2.27 mM-sodium n-butyrate in the presence of insulin (0.1 munit/ml). 3. The antidiabetic drug metformin (60.4 μM) had no effect on glucose uptake in the absence or presence of insulin (0.1 munit/ml), but stimulated uptake in the presence of 2.27 mM-sodium n-butyrate together with insulin (0.1 munit/ml). 4. It is concluded that the metabolic control of glucose uptake in human skeletal muscle is similar to that in rat heart and diaphragm, and that the preparation provides a useful model for biochemical and pharmacological investigations of glucose metabolism in skeletal muscle.

scholarly journals Endurance exercise training-responsive miR-19b-3p improves skeletal muscle glucose metabolism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Julie Massart ◽  
Rasmus J. O. Sjögren ◽  
Brendan Egan ◽  
Christian Garde ◽  
Magnus Lindgren ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Exercise Training ◽  
Aerobic Exercise ◽  
Glucose Uptake ◽  
Human Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Aerobic Exercise Training ◽  
Human Skeletal Muscle Cells

AbstractSkeletal muscle is a highly adaptable tissue and remodels in response to exercise training. Using short RNA sequencing, we determine the miRNA profile of skeletal muscle from healthy male volunteers before and after a 14-day aerobic exercise training regime. Among the exercise training-responsive miRNAs identified, miR-19b-3p was selected for further validation. Overexpression of miR-19b-3p in human skeletal muscle cells increases insulin signaling, glucose uptake, and maximal oxygen consumption, recapitulating the adaptive response to aerobic exercise training. Overexpression of miR-19b-3p in mouse flexor digitorum brevis muscle enhances contraction-induced glucose uptake, indicating that miR-19b-3p exerts control on exercise training-induced adaptations in skeletal muscle. Potential targets of miR-19b-3p that are reduced after aerobic exercise training include KIF13A, MAPK6, RNF11, and VPS37A. Amongst these, RNF11 silencing potentiates glucose uptake in human skeletal muscle cells. Collectively, we identify miR-19b-3p as an aerobic exercise training-induced miRNA that regulates skeletal muscle glucose metabolism.

scholarly journals Endothelin-1 Reduces Glucose Uptake in Human Skeletal Muscle In Vivo and In Vitro

Diabetes ◽  
2011 ◽  
Vol 60 (8) ◽  
pp. 2061-2067 ◽  
Author(s):  
A. Shemyakin ◽  
F. Salehzadeh ◽  
D. Esteves Duque-Guimaraes ◽  
F. Bohm ◽  
E. Rullman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Human Skeletal Muscle ◽  
Endothelin 1

scholarly journals Regulation of Glucose Uptake by Endothelin-1 in Human Skeletal Muscle in Vivo and in Vitro

2010 ◽  
Vol 24 (3) ◽  
pp. 679-680
Author(s):  
Alexey Shemyakin ◽  
Firoozeh Salehzadeh ◽  
Felix Böhm ◽  
Lubna Al-Khalili ◽  
Adrian Gonon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Human Skeletal Muscle ◽  
Endothelin 1

scholarly journals Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle

2017 ◽  
Vol 313 (4) ◽  
pp. E483-E491 ◽  
Author(s):  
Maxwell A. Ruby ◽  
Isabelle Riedl ◽  
Julie Massart ◽  
Marcus Åhlin ◽  
Juleen R. Zierath
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Muscle Metabolism ◽  
Whole Body ◽  
Skeletal Muscle Metabolism ◽  
Ampk Signaling

Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. Although Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo. PKN2 knockdown in vitro decreased insulin-stimulated glucose uptake, incorporation into glycogen, and oxidation. PKN2 siRNA increased 5′-adenosine monophosphate-activated protein kinase (AMPK) signaling while stimulating fatty acid oxidation and incorporation into triglycerides and decreasing protein synthesis. At the transcriptional level, PKN2 knockdown increased expression of PGC-1α and SREBP-1c and their target genes. In mature skeletal muscle, in vivo PKN2 knockdown decreased glucose uptake and increased AMPK phosphorylation. Thus, PKN2 alters key signaling pathways and transcriptional networks to regulate glucose and lipid metabolism. Identification of PKN2 as a novel regulator of insulin and AMPK signaling may provide an avenue for manipulation of skeletal muscle metabolism.

Insulin binding and sensitivity in rat skeletal muscle: effect of starvation

1981 ◽  
Vol 240 (2) ◽  
pp. E184-E190 ◽  
Author(s):  
L. J. Brady ◽  
M. N. Goodman ◽  
F. N. Kalish ◽  
N. B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Insulin Binding ◽  
The Other ◽  
Rat Skeletal Muscle ◽  
In Vitro Sensitivity

In contrast to adipose tissue and heart, the in vitro sensitivity of skeletal muscle to insulin is enhanced by starvation. To determine the basis for this, insulin binding and its ability to stimulate glucose metabolism were examined in the incubated rat soleus. In solei from 50-g rats, starvation for 48 h enhanced insulin binding by 50-100% at concentrations of 100 ng/ml or less. Starvation also resulted in higher basal and insulin-stimulated rates of glycogen synthesis, glycolysis, and glucose uptake. The enhanced effect of insulin only occurred at concentrations less than 50-75 ng/ml, in keeping with the increased binding of insulin in this concentration range. On the other hand, under conditions in which binding at equilibrium was the same, glucose uptake was still higher in the starved group, suggesting that some postreceptor event may have been more sensitive to insulin. These studies confirm that the in vitro sensitivity of rat skeletal muscle to insulin is enhanced by 48 h of starvation. They suggest that this is due at least partially to an increase in insulin binding at physiological concentrations.

Effect of AMPK activation on muscle glucose metabolism in conscious rats

1999 ◽  
Vol 276 (5) ◽  
pp. E938-E944 ◽  
Author(s):  
Raynald Bergeron ◽  
Raymond R. Russell ◽  
Lawrence H. Young ◽  
Jian-Ming Ren ◽  
Melissa Marcucci ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Additive Effect ◽  
Medial Gastrocnemius ◽  
Ampk Activation ◽  
Transport Activity ◽  
Muscle Glucose Transport

The effect of AMP-activated protein kinase (AMPK) activation on skeletal muscle glucose metabolism was examined in awake rats by infusing them with 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR; 40 mg/kg bolus and 7.5 mg ⋅ kg−1 ⋅ min−1constant infusion) along with a variable infusion of glucose (49.1 ± 2.4 μmol ⋅ kg−1 ⋅ min−1) to maintain euglycemia. Activation of AMPK by AICAR caused 2-deoxy-d-[1,2-3H]glucose (2-DG) uptake to increase more than twofold in the soleus and the lateral and medial gastrocnemius compared with saline infusion and occurred without phosphatidylinositol 3-kinase activation. Glucose uptake was also assessed in vitro by use of the epitrochlearis muscle incubated either with AICAR (0.5 mM) or insulin (20 mU/ml) or both in the presence or absence of wortmannin (1.0 μM). AICAR and insulin increased muscle 2-DG uptake rates by ∼2- and 2.7-fold, respectively, compared with basal rates. Combining AICAR and insulin led to a fully additive effect on muscle glucose transport activity. Wortmannin inhibited insulin-stimulated glucose uptake. However, neither wortmannin nor 8-(p-sulfophenyl)-theophylline (10 μM), an adenosine receptor antagonist, inhibited the AICAR-induced activation of glucose uptake. Electrical stimulation led to an about threefold increase in glucose uptake over basal rates, whereas no additive effect was found when AICAR and contractions were combined. In conclusion, the activation of AMPK by AICAR increases skeletal muscle glucose transport activity both in vivo and in vitro. This cellular pathway may play an important role in exercise-induced increase in glucose transport activity.

scholarly journals SUN-657 The Effect of Simvastatin on Glucose Metabolism in Primary Human Muscle Cells

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Selina Mäkinen ◽  
Neeta Datta-Sengupta ◽  
Yen Nguyen ◽  
Petro Kyrylenko ◽  
Markku Laakso ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Human Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Acid Form ◽  
Lactone Form ◽  
Human Skeletal Muscle Cells ◽  
Glucose Incorporation

Abstract Statin use, especially treatment with simvastatin, is associated with impaired insulin secretion and whole-body insulin sensitivity, and increased risk for T2D. Here, we investigated the direct effects of lactone- and acid-forms of simvastatin on glucose metabolism in primary human skeletal muscle cells. Exposure of human myotubes to lactone-form simvastatin for 48 h increased glucose uptake and glucose incorporation into glycogen, whereas the acid-form did not affect glucose uptake and decreased glucose incorporation into glycogen. These metabolic actions were accompanied by changes in insulin signaling, as phosphorylation of AS160 and GSK3β was upregulated with lactone-, but not with acid-form simvastatin. Exposure to both lactone and acid-forms of simvastatin led to a decrease in glycolysis and glycolytic capacity, as well as to a decrease in mitochondrial respiration and ATP production. Collectively these data indicate that lactone- and acid forms of simvastatin exhibit differences such that lactone-form increases, and acid-form impairs glucose incorporation into glycogen. Exposure to either form of simvastatin, however, impairs glycolysis and mitochondrial oxidative metabolism in human skeletal muscle cells.

scholarly journals Engineering a 3D in vitro model of human skeletal muscle at the single fiber scale

PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0232081 ◽  
Author(s):  
Anna Urciuolo ◽  
Elena Serena ◽  
Rusha Ghua ◽  
Susi Zatti ◽  
Monica Giomo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
In Vitro Model ◽  
Single Fiber ◽  
3D In Vitro Model ◽  
Vitro Model

scholarly journals Low-Dose Acrolein, an Endogenous and Exogenous Toxic Molecule, Inhibits Glucose Transport via an Inhibition of Akt-Regulated GLUT4 Signaling in Skeletal Muscle Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 7228
Author(s):  
Ching-Chia Wang ◽  
Huang-Jen Chen ◽  
Ding-Cheng Chan ◽  
Chen-Yuan Chiu ◽  
Shing-Hwa Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Urinary acrolein adduct levels have been reported to be increased in both habitual smokers and type-2 diabetic patients. The impairment of glucose transport in skeletal muscles is a major factor responsible for glucose uptake reduction in type-2 diabetic patients. The effect of acrolein on glucose metabolism in skeletal muscle remains unclear. Here, we investigated whether acrolein affects muscular glucose metabolism in vitro and glucose tolerance in vivo. Exposure of mice to acrolein (2.5 and 5 mg/kg/day) for 4 weeks substantially increased fasting blood glucose and impaired glucose tolerance. The glucose transporter-4 (GLUT4) protein expression was significantly decreased in soleus muscles of acrolein-treated mice. The glucose uptake was significantly decreased in differentiated C2C12 myotubes treated with a non-cytotoxic dose of acrolein (1 μM) for 24 and 72 h. Acrolein (0.5–2 μM) also significantly decreased the GLUT4 expression in myotubes. Acrolein suppressed the phosphorylation of glucose metabolic signals IRS1, Akt, mTOR, p70S6K, and GSK3α/β. Over-expression of constitutive activation of Akt reversed the inhibitory effects of acrolein on GLUT4 protein expression and glucose uptake in myotubes. These results suggest that acrolein at doses relevant to human exposure dysregulates glucose metabolism in skeletal muscle cells and impairs glucose tolerance in mice.

scholarly journals Effects of Oral Resveratrol Supplementation on Glycogen Replenishment and Mitochondria Biogenesis in Exercised Human Skeletal Muscle

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3721
Author(s):  
Chun-Ching Huang ◽  
Chia-Chen Liu ◽  
Jung-Piao Tsao ◽  
Chin-Lin Hsu ◽  
I-Shiung Cheng
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Human Skeletal Muscle ◽  
Young Male ◽  
Gene Expressions ◽  
Plasma Parameters ◽  
Post Exercise ◽  
Glycogen Resynthesis ◽  
Mitochondria Biogenesis

The present study aimed to investigate the effect of oral resveratrol supplementation on the key molecular gene expressions involved in mitochondria biogenesis and glycogen resynthesis in human skeletal muscle. Nine young male athletes participated in the single-blind and crossover designed study. All subjects completed a 4-day resveratrol and placebo supplement in a randomized order while performing a single bout of cycling exercise. Immediately after the exercise challenge, the subjects consumed a carbohydrate (CHO) meal (2 g CHO/Kg body mass) with either resveratrol or placebo capsules. Biopsied muscle samples, blood samples and expired gas samples were obtained at 0 h and 3 h after exercise. The muscle samples were measured for gene transcription factor expression by real-time PCR for glucose uptake and mitochondria biogenesis. Plasma glucose, insulin, glycerol, non-esterified fatty acid concentrations and respiratory exchange ratio were analyzed during post-exercise recovery periods. The results showed that the muscle glycogen concentrations were higher at 3 h than at 0 h; however, there were no difference between resveratrol trial and placebo trial. There were no significantly different concentrations in plasma parameters between the two trials. Similarly, no measured gene expressions were significant between the two trials. The evidence concluded that the 4-day oral resveratrol supplementation did not improve post-exercise muscle glycogen resynthesis and related glucose uptake and mitochondrial biosynthesis gene expression in men.

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