Insulin-induced Hypoglycemia in a Mouse Model: Association of Inflammatory Markers with Liver and Kidney Injury

The aim of this study was to evaluate the early histopathological and inflammatory effects of acute insulin-induced hypoglycemia in liver and kidney tissues. Acute hypoglycemia was experimentally induced by insulin administration, and liver and kidney samples were analyzed histologically. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nuclear factor kappa B (NF-κB) protein expression were assessed by immunohistochemistry, while TNF-α and IL-6 gene expression were evaluated using reverse transcription quantitative polymerase chain reaction. Acute hypoglycemia induced early structural alterations in both organs, with more pronounced and progressive changes observed in the kidney. Renal injury included tubular epithelial degeneration, tubular dilatation, and glomerular alterations, whereas hepatic changes were milder and mainly characterized by sinusoidal dilatation and hyperemia. No significant differences were observed in TNF-α, IL-6, or NF-κB protein expression. However, renal TNF-α and IL-6 messenger RNA levels showed transient alterations over time. In conclusion, acute insulin-induced hypoglycemia leads to early structural injury in liver and kidney tissues, with greater susceptibility observed in the kidney. These changes occur in the absence of significant inflammatory protein activation, suggesting that early tissue injury is primarily driven by metabolic stress rather than overt inflammatory signaling, although transient transcriptional responses may precede detectable protein-level changes.