Metformin increases the PGC-1α protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo

2006 ◽  
Vol 101 (6) ◽  
pp. 1685-1692 ◽  
Author(s):  
Masataka Suwa ◽  
Toru Egashira ◽  
Hiroshi Nakano ◽  
Haruka Sasaki ◽  
Shuzo Kumagai
Keyword(s):  
Skeletal Muscle ◽  
Enzyme Activities ◽  
Oxidative Enzyme ◽  
Ampk Phosphorylation

scholarly journals Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM

1997 ◽  
Vol 83 (1) ◽  
pp. 166-171 ◽  
Author(s):  
Jean-Aimé Simoneau ◽  
David E. Kelley
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Enzyme Activities ◽  
Glycolytic Enzymes ◽  
Oxidative Enzyme ◽  
Oxidative Enzymes ◽  
Glucose Tolerant

Simoneau, Jean-Aimé, and David E. Kelley. Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. J. Appl. Physiol. 83(1): 166–171, 1997.—The insulin resistance of skeletal muscle in glucose-tolerant obese individuals is associated with reduced activity of oxidative enzymes and a disproportionate increase in activity of glycolytic enzymes. Because non-insulin-dependent diabetes mellitus (NIDDM) is a disorder characterized by even more severe insulin resistance of skeletal muscle and because many individuals with NIDDM are obese, the present study was undertaken to examine whether decreased oxidative and increased glycolytic enzyme activities are also present in NIDDM. Percutaneous biopsy of vatus lateralis muscle was obtained in eight lean (L) and eight obese (O) nondiabetic subjects and in eight obese NIDDM subjects and was assayed for marker enzymes of the glycolytic [phosphofructokinase, glyceraldehyde phosphate dehydrogenase, hexokinase (HK)] and oxidative pathways [citrate synthase (CS), cytochrome- c oxidase], as well as for a glycogenolytic enzyme (glycogen phosphorylase) and a marker of anaerobic ATP resynthesis (creatine kinase). Insulin sensitivity was measured by using the euglycemic clamp technique. Activity for glycolytic enzymes (phosphofructokinase, glyceraldehye phosphate dehydrogenase, HK) was highest in subjects with subjects with NIDDM, following the order of NIDDM > O > L, whereas maximum velocity for oxidative enzymes (CS, cytochrome- c oxidase) was lowest in subjects with NIDDM. The ratio between glycolytic and oxidative enzyme activities within skeletal muscle correlated negatively with insulin sensitivity. The HK/CS ratio had the strongest correlation ( r = −0.60, P < 0.01) with insulin sensitivity. In summary, an imbalance between glycolytic and oxidative enzyme capacities is present in NIDDM subjects and is more severe than in obese or lean glucose-tolerant subjects. The altered ratio between glycolytic and oxidative enzyme activities found in skeletal muscle of individuals with NIDDM suggests that a dysregulation between mitochondrial oxidative capacity and capacity for glycolysis is an important component of the expression of insulin resistance.

scholarly journals AMPK Phosphorylation Effect of Genistein Is Independent of GPR30

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 484-484
Author(s):  
Sarai Vásquez-Reyes ◽  
Ariana Vargas-Castillo ◽  
Jose C Crispin ◽  
Florencia Rosetti ◽  
Nimbe Torres ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Composition ◽  
Oxygen Consumption ◽  
Weight Gain ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Wild Type ◽  
Ampk Phosphorylation

Abstract Objectives Genistein promotes fatty acid oxidation, improves glucose tolerance and increases energy expenditure. These effects are associated with AMPK phosphorylation in skeletal muscle. However, the molecular mechanism by which genistein activates the signaling pathway to activate AMPK phosphorylation is not yet known. Several target proteins have been suggested, one o them is GPR30, but it has not been studied. Thus, the aim of this study was to determine if AMPK phosphorylation by genistein is activated by GPR30. Methods To determine if GPR30 is involved in the mechanism that promotes AMPK phosphorylation we used C2C12 GPR30 KD (knock down) myotubes obtained by transduction with a shRNA, and also GPR30 −/− primary myotubes. AMPK phosphorylation was determined via western blot in the presence of genistein after 1 hour in both cultures. Furthermore, in order to establish in vivo if the beneficial effects of genistein were associated to GPR30, C57BL/6 mice (wild type WT) and GPR30 −/− mice were fed with both control and high fat sucrose diets (HFSD) containing genistein for 2 months. During two months of treatment, weight gain, food consumption, and body composition were measured as well as a glucose tolerance test (GTT), indirect calorimetry and AMPK phosphorylation by western blot in skeletal muscle of all of groups. Results Genistein at concentrations of 0.3,1,3 and 10µM increased AMPK phosphorylation in GPR30 KD, and GPR30 −/− primary myotubes, indicating that GPR30 is not directly involved in AMPK phosphorylation by genistein in an in vitro model. The in vivo study showed that the effect of genistein in GPR30 −/− mice on weight gain, body composition, GTT and indirect calorimetry was similar compared to wild type mice. The mice that consumed a HFSD with genistein gained less weight and less body fat, regardless of genotype (WT or GPR30 −/−). Similar effects were observed in the glucose tolerance test, oxygen exchange coefficient and oxygen consumption. Wild type and GPR30 −/− mice that consumed genistein had a better glucose tolerance than those that did not consume genistein. Conclusions This study showed that GPR30 its not directly involved in promoting AMPK phosphorylation by genistein. In addition, genistein reduced weight gain, increased glucose tolerance and increased oxygen consumption even in the absence of GPR30. Funding Sources INCMNSZ.

Effects of Chronic Ethanol Abuse on Structure and Enzyme Activities of Skeletal Muscle in Man

1975 ◽  
Vol 35 (6) ◽  
pp. 601-607 ◽  
Author(s):  
K. -H. Kiessling ◽  
L. Pilström ◽  
A. -C. Bylund ◽  
K. Piehl ◽  
B. Saltin
Keyword(s):  
Skeletal Muscle ◽  
Enzyme Activities ◽  
Chronic Ethanol ◽  
Ethanol Abuse

scholarly journals Modelling the skeletal muscle injury recovery using in vivo contrast-enhanced micro-CT: a proof-of-concept study in a rat model

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Bruno Paun ◽  
Daniel García Leon ◽  
Alex Claveria Cabello ◽  
Roso Mares Pages ◽  
Elena de la Calle Vargas ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Rat Model ◽  
Muscle Injury ◽  
Micro Ct ◽  
Skeletal Muscle Injury ◽  
Monitoring Time ◽  
Contrast Enhanced Ct ◽  
Contrast Enhanced ◽  
Injury Recovery

Abstract Background Skeletal muscle injury characterisation during healing supports trauma prognosis. Given the potential interest of computed tomography (CT) in muscle diseases and lack of in vivo CT methodology to image skeletal muscle wound healing, we tracked skeletal muscle injury recovery using in vivo micro-CT in a rat model to obtain a predictive model. Methods Skeletal muscle injury was performed in 23 rats. Twenty animals were sorted into five groups to image lesion recovery at 2, 4, 7, 10, or 14 days after injury using contrast-enhanced micro-CT. Injury volumes were quantified using a semiautomatic image processing, and these values were used to build a prediction model. The remaining 3 rats were imaged at all monitoring time points as validation. Predictions were compared with Bland-Altman analysis. Results Optimal contrast agent dose was found to be 20 mL/kg injected at 400 μL/min. Injury volumes showed a decreasing tendency from day 0 (32.3 ± 12.0mm3, mean ± standard deviation) to day 2, 4, 7, 10, and 14 after injury (19.6 ± 12.6, 11.0 ± 6.7, 8.2 ± 7.7, 5.7 ± 3.9, and 4.5 ± 4.8 mm3, respectively). Groups with single monitoring time point did not yield significant differences with the validation group lesions. Further exponential model training with single follow-up data (R2 = 0.968) to predict injury recovery in the validation cohort gave a predictions root mean squared error of 6.8 ± 5.4 mm3. Further prediction analysis yielded a bias of 2.327. Conclusion Contrast-enhanced CT allowed in vivo tracking of skeletal muscle injury recovery in rat.

scholarly journals Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 481
Author(s):  
Gemma G. Martínez-García ◽  
Raúl F. Pérez ◽  
Álvaro F. Fernández ◽  
Sylvere Durand ◽  
Guido Kroemer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Mammalian Cells ◽  
Tissue Homeostasis ◽  
In Vivo Studies ◽  
Protective Mechanism ◽  
Cardiac Damage ◽  
Wide Range ◽  
First Time

Autophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies, an increasing number of in vivo studies involving animal models targeting autophagy genes have been developed. In mammals, total autophagy inactivation is lethal, and constitutive knockout models lacking effectors of this route are not viable, which has hindered so far the analysis of the consequences of a systemic autophagy decline. Here, we take advantage of atg4b−/− mice, an autophagy-deficient model with only partial disruption of the process, to assess the effects of systemic reduction of autophagy on the metabolome. We describe for the first time the metabolic footprint of systemic autophagy decline, showing that impaired autophagy results in highly tissue-dependent alterations that are more accentuated in the skeletal muscle and plasma. These changes, which include changes in the levels of amino-acids, lipids, or nucleosides, sometimes resemble those that are frequently described in conditions like aging, obesity, or cardiac damage. We also discuss different hypotheses on how impaired autophagy may affect the metabolism of several tissues in mammals.

scholarly journals Consequences of SUR2[A478V] Mutation in Skeletal Muscle of Murine Model of Cantu Syndrome

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1791
Author(s):  
Rosa Scala ◽  
Fatima Maqoud ◽  
Nicola Zizzo ◽  
Giuseppe Passantino ◽  
Antonietta Mele ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Katp Channel ◽  
Ex Vivo ◽  
Channel Modulation ◽  
Flexor Digitorum Brevis ◽  
Inflammatory Edema ◽  
Flexor Digitorum ◽  
Channel Currents

(1) Background: Cantu syndrome (CS) arises from gain-of-function (GOF) mutations in the ABCC9 and KCNJ8 genes, which encode ATP-sensitive K+ (KATP) channel subunits SUR2 and Kir6.1, respectively. Most CS patients have mutations in SUR2, the major component of skeletal muscle KATP, but the consequences of SUR2 GOF in skeletal muscle are unknown. (2) Methods: We performed in vivo and ex vivo characterization of skeletal muscle in heterozygous SUR2[A478V] (SUR2wt/AV) and homozygous SUR2[A478V] (SUR2AV/AV) CS mice. (3) Results: In SUR2wt/AV and SUR2AV/AV mice, forelimb strength and diaphragm amplitude movement were reduced; muscle echodensity was enhanced. KATP channel currents recorded in Flexor digitorum brevis fibers showed reduced MgATP-sensitivity in SUR2wt/AV, dramatically so in SUR2AV/AV mice; IC50 for MgATP inhibition of KATP currents were 1.9 ± 0.5 × 10−5 M in SUR2wt/AV and 8.6 ± 0.4 × 10−6 M in WT mice and was not measurable in SUR2AV/AV. A slight rightward shift of sensitivity to inhibition by glibenclamide was detected in SUR2AV/AV mice. Histopathological and qPCR analysis revealed atrophy of soleus and tibialis anterior muscles and up-regulation of atrogin-1 and MuRF1 mRNA in CS mice. (4) Conclusions: SUR2[A478V] “knock-in” mutation in mice impairs KATP channel modulation by MgATP, markedly so in SUR2AV/AV, with atrophy and non-inflammatory edema in different skeletal muscle phenotypes.

Enzyme studies of skeletal muscle in mice with hereditary muscular dystrophy

1963 ◽  
Vol 205 (5) ◽  
pp. 897-901 ◽  
Author(s):  
Marilyn W. McCaman
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Glutathione Reductase ◽  
Enzyme Activities ◽  
Lactic Dehydrogenase ◽  
Normal Muscle ◽  
Dystrophic Muscle ◽  
Nerve Section ◽  
Mouse Muscle ◽  
Dystrophic Mouse

The activities of 20 enzymes in normal, heterozygous, and dystrophic mouse muscle were studied by means of quantitative microchemical methods. Enzyme activities in normal and heterozygous muscle were essentially the same. In dystrophic muscle glucose-6-P dehydrogenase, 6-P-gluconic dehydrogenase, glutathione reductase, peptidase, ß-glucuronidase, and glucokinase activities were significantly higher than in normal muscle, while α-glycero-P dehydrogenase and lactic dehydrogenase activities were significantly lower. The pattern of enzyme activities found in normal gastrocnemius denervated by nerve section was strikingly similar to that in dystrophic muscle.

Sign in / Sign up

Export Citation Format

Share Document