Organotins (OTs) are considered some of the most toxic chemicals introduced into aquatic environments by anthropogenic activities. They are widely used for agricultural and industrial purposes and as antifouling additives on boat hull’s paints. Even though the use of OTs was banned in 2008, elevated levels of OTs can still be detected in aquatic environments. OTs’ deleterious effects upon wildlife and experimental animals are well documented and include endocrine disruption, immunotoxicity, neurotoxicity, genotoxicity, and metabolic dysfunction. Crustaceans are key members of zooplankton and benthic communities and have vital roles in food chains, so the endocrine-disrupting effects of tributyltin (TBT) on crustaceans can affect other organisms. TBT can disrupt carbohydrate and lipid homeostasis of crustaceans by interacting with retinoid X receptor (RXR) and crustacean hyperglycemic hormone (CHH) signaling. Moreover, it can also interact with other nuclear receptors, disrupting methyl farnesoate and ecdysteroid signaling, thereby altering growth and sexual maturity, respectively. This compound also interferes in cytochrome P450 system disrupting steroid synthesis and reproduction. Crustaceans are also important fisheries worldwide, and its consumption can pose risks to human health. However, some questions remain unanswered. This mini review aims to update information about the effects of OTs on the metabolism, growth, and reproduction of crustaceans; to compare with known effects in mammals; and to point aspects that still needs to be addressed in future studies. Since both macrocrustaceans and microcrustaceans are good models to study the effects of sublethal TBT contamination, novel studies should be developed using multibiomarkers and omics technology.

Type 1 diabetes mellitus is a prevalent autoimmune disease worldwide. The knowledge of female particularities in metabolic dysfunction is of fundamental importance, leading to better choices for human therapy candidates. The aim of this study is to investigate the glucose flux peculiarities of female rats submitted to two classic experimental diabetes protocols. Female Wistar rats, 60 days old, were used to evaluate biochemical and hormonal serum parameters, in addition to skeletal muscle and liver energy stocks and ¹⁴C-glucose and ¹⁴C-alanine flux. Two different protocols, multiple (25 mg/kg dose) and single (65 mg/kg dose) intraperitoneal streptozotocin, were compared considering the alterations presented 48 h and 30 days after the drug administration. The results showed few indicators of muscle and liver metabolic imbalance. High-single streptozotocin dose promoted 97% and 41% lower glycogen levels in liver and muscle respectively. Multiple-low streptozotocin dose promoted 63% lower lipid synthesis in liver. After 30 days, diabetic animals presented hyperglycaemia in both protocols, 589.5 (529.3/642.3) mg/dL to high-single dose and 374.2 (339.3/530.6) mg/dL to multiple-low dose. However, they did not present lower insulin levels, alterations on muscle glucose uptake, nor higher hepatic gluconeogenesis. In conclusion, this study demonstrates that females, at least Wistar rats, are less responsive to classic diabetes protocols established in literature, so mechanisms of experimental diabetes for females need more investigation. After which, therapeutic candidates should be evaluated in such a way sex bias does not present itself as a factor that hinders reproducibility in human studies.

GLP-1 receptor agonists have emerged as key pharmacological tools in the treatment of type 2 diabetes and obesity. While their anorexigenic effects are well characterized, the mechanisms by which GLP-1 modulates pancreatic β-cell function remain only partially understood. In this article, we argue that GLP-1 receptor agonists should be viewed as integrative regulators of β-cell function and explore the multifaceted actions of GLP-1 analogs on β-cell signaling. GLP-1 influences key secretagogues and intracellular mediators (calcium, glutamate, γ-aminobutyric acid, serotonin, and urocortin-3), with complex roles in insulin exocytosis. Additionally, we discuss the interplay between calcium and cAMP, and how GLP-1 modulates both pathways to coordinate insulin secretion. Emerging evidence suggests that GLP-1 analogs affect mitochondrial morphology and redox homeostasis. Considering the relatively low expression of classical antioxidant enzymes in β-cells, and their reliance on both glycolytic and mitochondrial metabolism to sustain insulin secretion, the influence of GLP-1 on mitochondrial dynamics and reactive oxygen species may play a central role in sustaining cell function and viability. Despite recent advances, critical gaps persist in the literature, particularly regarding organelle cross talk, intracellular calcium stores, and the modulation of vesicular content. Drawing on current evidence, we propose that three mechanistic dimensions (intracellular neurotransmitters, mitochondrial remodeling, and redox control) represent key areas where clarifying GLP-1 actions could most effectively advance the field. Further investigation into these mechanisms is essential for a comprehensive understanding of GLP-1 actions in β-cells. This knowledge may help refine current incretin-based therapies and identify novel molecular targets for the treatment of metabolic disorders. Article Highlights: GLP-1 and its analogs enhance insulin secretion, but the specific intracellular mechanisms in β-cells remain unclear. Key intracellular mediators including calcium, glutamate, γ-aminobutyric acid, serotonin, and urocortin-3 are modulated by GLP-1 signaling with variable and sometimes contradictory effects. GLP-1 may affect mitochondrial dynamics and redox balance in β-cells, both critical for function and survival. Gaps in knowledge remain regarding cross talk between classical secretagogues and GLP-1 pathways. Further investigation is needed to clarify how GLP-1 integrates metabolic, signaling, and organelle-based processes in insulin secretion.

Introduction and objectives: Obesity represents a major global public health problem. Its etiology is multifactorial and includes poor dietary habits, such as hypercaloric and hyperlipidic diets (HFDs), physical inactivity, and genetic factors. Regular exercise is, per se, a tool for the treatment and prevention of obesity, and recent studies suggest that the beneficial effects of exercise can be potentiated by the fasting state, thus potentially promoting additional effects. Despite the significant number of studies showing results that corroborate such hypothesis, very few have evaluated the effects of fasted-state exercise in overweight/obese populations. Therefore, the aim of this study was to evaluate the subacute effects (12 h after conclusion) of a single moderate-intensity exercise bout, performed in either a fed or an 8 h fasted state, on serum profile, substrate-content and heat shock pathway–related muscle protein immunocontent in obese male rats. Methods: Male Wistar rats received a modified high-fat diet for 12 weeks to induce obesity and insulin resistance. The animals were allocated to four groups: fed rest (FER), fed exercise (FEE), fasted rest (FAR) and fasted exercise (FAE). The exercise protocol was a 30 min session on a treadmill, with an intensity of 60% of VO₂max. The duration of the fasting period was 8 h prior to the exercise session. After a 12 h recovery, the animals were killed and metabolic parameters of blood, liver, heart, gastrocnemius and soleus muscles were evaluated, as well as SIRT1 and HSP70 immunocontent in the muscles. Results: HFD induced obesity and insulin resistance. Soleus glycogen concentration decreased in the fasted groups and hepatic glycogen decreased in the fed exercise group. The combination of exercise and fasting promoted a decreased concentration of serum total cholesterol and triglycerides. In the heart, combination fasting plus exercise was able to decrease triglycerides to control levels. In the soleus muscle, both fasting and fasting plus exercise were able to decrease triglyceride concentrations. In addition, heat shock protein 70 and sirtuin 1 immunocontent increased after exercise in the gastrocnemius and soleus muscles. Conclusions: An acute bout of moderate intensity aerobic exercise, when realized in fasting, may induce, in obese rats with metabolic dysfunctions, beneficial adaptations to their health, such as better biochemical and molecular adaptations that last for at least 12 h. Considering the fact that overweight/obese populations present an increased risk of cardiovascular events/diseases, significant reductions in such plasma markers of lipid metabolism are an important achievement for these populations.

Background: Physical inactivity induces insulin resistance (IR) and metabolic imbalances before any significant changes in adiposity. Recent studies suggest that the beneficial effects of exercise can be potentiated if performed while fasting. This work aimed to compare the subacute effects of fed- and fasted-state single-bout exercise on biochemical parameters and cellular signaling in the metabolism. Methods: The animals were allocated into fed rest (FER), fasting rest (FAR), fed exercise (FEE), and fasting exercise (FAE) groups. The exercise protocol was a 30 min treadmill session at 60% of $\dot{\mathrm{V}}$O_2max. The fasting groups fasted for 8 h before exercise and were killed after 12 h post-exercise. Results: Soleus glycogen concentration increased only in the fasting groups, whereas the triglyceride (TGL) content increased in brown adipose tissue (BAT) and liver in the FAE. The FAE showed decreased plasma total cholesterol concentration compared withthe FAR group. Immunocontent of HSP70, SIRT1, UCP-1, and PGC1-α did not change in any tissue investigated. Conclusions: Our results indicate that physical exercise while fasting can have beneficial metabolic effects on sedentary animals. Remarkably, in the FAE group, there was a reduction in total plasma cholesterol and an increase in the capacity of BAT to metabolize and store nutrients in the form of TGLs.