Skeletal muscle plays a major role in whole‐body glucose metabolism. Insulin resistance in skeletal muscle is characterized by decreased insulin‐stimulated glucose uptake resulting from impaired intracellular trafficking and decreased glucose transporter 4 (GLUT4) expression. In this study, we illustrated that tilorone, a low‐molecular‐weight antiviral agent, improves glucose uptake in vitro and in vivo. Tilorone increased bone morphogenetic protein (BMP) signaling in C2C12 myoblasts, the transcription of multiple BMPs (BMP2, BMP4, BMP7, and BMP14), Smad4 expression, and the phosphorylation of BMP‐mediated Smad1/5/8. The activation of Akt2/AS160 (TBC1D4) signaling, the critical regulator of GLUT4 translocation, was also increased, as well as the levels of GLUT4 and GLUT1, leading to enhanced uptake of the radioactively labeled glucose analog ¹⁸F‐fluoro‐2‐deoxyglucose (¹⁸FDG). However, this excess glucose content did not result in increased ATP formation by mitochondrial respiration; both basal and ATP‐linked respiration were diminished, thereby contributing to the induction of AMPK. In differentiated myotubes, AS160 phosphorylation and ¹⁸FDG uptake also increased. Moreover, tilorone administration further increased insulin‐stimulated phosphorylation of Akt2 and glucose uptake of myotubes indicating an insulin‐sensitizing effect. Importantly, during in vivo experiments, the systemic administration of tilorone resulted in increased ¹⁸FDG uptake of skeletal muscle, liver, and adipose tissue in C57BL/6 mice. Our results provide new perspectives for the treatment of type 2 diabetes, which has a limited number of treatments that regulate protein expression or translocation.

Many effects of polyamines (PAs) are well known in plant developmental processes; however, the significance of their catabolism is not well understood. Copper amine oxidase (CuAO) is involved in the degradation of diamine putrescine (Put). The genotype dependence and time-dependent effects of this enzyme are rarely examined, so this study aims to discover the role of CuAO in tomato genotypes in different stages of seedling development. Exogenously applied L-aminoguanidine (AG), a CuAO inhibitor, was used to decrease the activity of CuAOs. Based on our results, it can be concluded that there is a genotype dependence of Put degradation, and AG treatment caused a long-term shift of PA catabolism by changing the activities of polyamine oxidase (PAO), catalyzing the degradation of higher PAs. Our results demonstrate that the modification of PA catabolism could have long-term results in polyamine metabolism in different tomato genotypes.

The remodelling of the extracellular matrix plays an important role in skeletal muscle development and regeneration. Syndecan-4 is a cell surface proteoglycan crucial for muscle differentiation. Syndecan-4^−/− mice have been reported to be unable to regenerate following muscle damage. To investigate the consequences of the decreased expression of Syndecan-4, we have studied the in vivo and in vitro muscle performance and the excitation–contraction coupling machinery in young and aged Syndecan-4^+/− (SDC4) mice. In vivo grip force was decreased significantly as well as the average and maximal speed of voluntary running in SDC4 mice, regardless of their age. The maximal in vitro twitch force was reduced in both EDL and soleus muscles from young and aged SDC4 mice. Ca²⁺ release from the sarcoplasmic reticulum decreased significantly in the FDB fibres of young SDC4 mice, while its voltage dependence was unchanged regardless of age. These findings were present in muscles from young and aged mice as well. On C2C12 murine skeletal muscle cells, we have also found altered calcium homeostasis upon Syndecan-4 silencing. The decreased expression of Syndecan-4 leads to reduced skeletal muscle performance in mice and altered motility in C2C12 myoblasts via altered calcium homeostasis. The altered muscle force performance develops at an early age and is maintained throughout the life course of the animal until old age.

L-aminoguanidine (AG) is an inhibitor frequently used for investigating plant abiotic stress responses; however, its exact mode of action is not well understood. Many studies used this compound as a specific diamine oxidase inhibitor, whereas other studies used it for reducing nitric oxide (NO) production. Recent studies suggest its antiglycation effect; however, this remains elusive in plants. This review summarises our current knowledge about different targets of AG in plants. Our recommendation is to use AG as a modulator of polyamine-related mechanisms rather than a specific inhibitor. In the future overall investigation is needed to decipher the exact mechanisms of AG. More careful application of AG could give more insight into plant abiotic stress responses.

Several clinical studies indicate that smoking predisposes its consumers to esophageal inflammatory and malignant diseases, but the cellular mechanism is not clear. Ion transporters protect esophageal epithelial cells by maintaining intracellular pH at normal levels. In this study, we hypothesized that smoking affects the function of ion transporters, thus playing a role in the development of smoking-induced esophageal diseases. Esophageal cell lines were treated with cigarettesmoke extract (CSE), and the viability and proliferation of the cells, as well as the activity, mRNA and protein expression of the Na⁺/H⁺ exchanger-1 (NHE-1), were studied. NHE-1 expression was also investigated in human samples. For chronic treatment, guinea pigs were exposed to tobacco smoke, and NHE-1 activity was measured. Silencing of NHE-1 was performed by using specific siRNA. CSE treatment increased the activity and protein expression of NHE-1 in the metaplastic cells and decreased the rate of proliferation in a NHE-1-dependent manner. In contrast, CSE increased the proliferation of dysplastic cells independently of NHE-1. In the normal cells, the expression and activity of NHE-1 decreased due to in vitro and in vivo smoke exposure. Smoking enhances the function of NHE-1 in Barrett’s esophagus, and this is presumably a compensatory mechanism against this toxic agent.

The endocannabinoid system (ECS) is known to regulate crucial bodily functions, including healthy muscle activity. However, its precise roles in normal skeletal muscle function and the development of muscle disorders remain unclear. Previously, we developed a tamoxifen-inducible, skeletal muscle-specific CB₁ receptor knockdown (skmCB1-KD) mouse model using the Cre/LoxP system. In this study, we aimed to clarify the mechanisms behind the observed reduction in muscle force generation in these mice. To investigate this, we analyzed calcium dynamics following electrical stimulation-induced muscle fatigue, assessed store-operated calcium entry (SOCE), and performed functional analysis of mitochondrial respiration. Our findings suggest that the reduced muscle performance observed in vivo likely arises from interconnected alterations in ATP production by mitochondria. Moreover, in skmCB1-KD mice, we detected a significant decrease in a component of the respiratory chain (complex IV) and a slowed dissipation of mitochondrial membrane potential upon the addition of an un-coupler (FCCP).