Interleukin-1 Receptor-Induced Nitric Oxide Production in the Pancreas Controls Hyperglycemia Caused by Scorpion Envenomation

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.

Scorpion envenomation in Brazil: Current scenario and perspectives for containing an increasing health problem

“…The scientific knowledge on scorpions regarding their ecology [166][167][168][169][170][171], venom composition [172][173][174][175], envenomation pathophysiology [176][177][178][179][180], and treatment options [181] has much advanced in the past years. However, in this same period, the number of scorpion accidents and the geographical distribution of several noxious species has substantially increased in Brazil.…”

Flavonoids Biosynthesis in Plants as a Defense Mechanism: Role and Function Concerning Pharmacodynamics and Pharmacokinetic Properties

“…A diabetic dietary supplement is B's Fisetin. A flavonoid called morin may be found in wine, fruits, Prunus dulcis, and Psidium guajava [163][164][165]. Morin, which has anti-inflammatory properties and is useful in treating inflammatory illnesses, was demonstrated by Heeba et al [166] to lower the cytokines IL-1, IL-6, and TNF in diabetic mice when administered at a dose of 30 mg/kg body weight.…”

Animal Venoms and Their Components: Molecular Mechanisms of Action

“…Thus, a life-threatening transitory hyperglycemia is among the Tityus serrulatus scorpion's envenomation effects. The study aimed to investigate that hyperglycemia due to scorpion envenomation may involve inflammatory signaling in the pancreas showed that T. serrulatus venom indeed induced the production of IL-1α and IL-1β in the pancreas, which provoked nitric oxide (NO) production and edema in β-cells in islets [13]. The authors suggest that a supportive therapy with inhibitors of NO production may help to prevent fatal outcomes of scorpion envenomation.…”