Abstract
Tityus serrulatus causes numerous scorpion envenomation accidents and deaths worldwide. The symptoms vary from local to systemic manifestations, culminating in pulmonary edema and cardiogenic shock. Among these events, transitory hyperglycemia is a severe manifestation that influences pulmonary edema, hemodynamic alterations, and cardiac disturbances. However, the molecular mechanism that leads to increased glucose levels after T. serrulatus envenomation remains unknown. This study aimed to investigate our hypothesis that hyperglycemia due to scorpion envenomation involves inflammatory signaling in the pancreas. The present study showed that T. serrulatus venom induces the production of IL-1α and IL-1β in the pancreas, which signal via IL-1R and provoke nitric oxide (NO) production as well as edema in β-cells in islets. Il1r1−/− mice were protected from transitory hyperglycemia and did not present disturbances in insulin levels in the serum. These results suggest that the pathway driven by IL-1α/IL-1β-IL-1R-NO inhibits insulin release by β-cells, which increases systemic glucose concentration during severe scorpion envenomation. A supportive therapy that inhibits NO production, combined with antiserum, may help to prevent fatal outcomes of scorpion envenomation. Our findings provide novel insights into the design of supportive therapy with NO inhibitors combined with antiscorpion venom serum to overcome fatal outcomes of scorpion envenomation.
Highlights
Scorpion envenomation is a serious public health problem in tropical countries [1]
This study investigated whether this signaling axis impacts insulin secretion and glycemia during scorpion envenomation in mice
Consistent with this phenotype, WT mice presented reduced levels of insulin in serum, whereas Il1r1−/− animals exhibited preserved insulin production in response to scorpion envenomation (Figure 1B). These results suggested that an IL-1R-dependent mechanism regulates insulin secretion and has a significant impact on glucose levels upon scorpion envenomation
Summary
Scorpion envenomation is a serious public health problem in tropical countries [1]. In Brazil, the number of accidents caused by these arthropods is higher than the number of accidents caused by all other venomous animals combined [2]. Tityus serrulatus (Ts) is the most prominent species in this scenario, because this scorpion is highly adapted to urban centers and reproduces by parthenogenesis [3]. Chemical control of scorpions is still a challenge. Scorpion stings result in a wide range of symptoms, classified as minor, mild, and severe [1]. Most cases of scorpion envenomation culminate in minor manifestations, which include only
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