Background: Persistent low-grade inflammation is a hallmark of type 2 diabetes (T2D), a chronic disease that poses a serious threat to health and leads to the gradual degeneration of islets pancreatic β-cells. The purpose of the current study was to assess how the inflammatory environment affected the expression of NADPH oxidase 2 (NOX2) in the pancreatic islets of diabetic rats and to investigate the connections between NOX2 activity and systemic inflammatory markers. Methods: Male Wistar rats weighing 250 - 300 g and aged 8 - 10 weeks were given an intraperitoneal injection of streptozotocin (50 mg/kg) to induce diabetes. After being separated by enzymatic digestion using collagenase P and purified using a Ficoll gradient, pancreatic islets were cultivated and incubated for 24 hours at different glucose concentrations (5.5 mM, 15 mM, and 25 mM). Apocynin and diphenyleneiodonium (5, 15, 25 μM) were used to pharmacologically inhibit NOX2. Following that, ELISA and immunoturbidimetry methods were used to measure the levels of NOX2, interleukin-6, and CRP. Results: The study showed that NOX2 activity increased in response to rising glucose concentrations in a dose-dependent manner. At 25 mM, a notable peak was seen (p < 0.01 vs. 5.5 mM), suggesting a marked rise in NOX2 activity at this concentration. This activation was accompanied by a proportional elevation of inflammatory markers in which IL-6 demonstrated an approximately eight-fold increase from baseline levels, while CRP exhibited a comparable progression. Pharmacological inhibition of NOX2 by both DPI and apocynin reduced significantly its enzymatic activity, IL-6 and CRP levels. Both NOX2 and CRP (r = 0.41, p = 0.1) and NOX2 and IL-6 (r = 0.41, p = 0.2) showed moderate but non-significant correlations. Conclusion: This study shows that in the pancreatic islets of diabetic rats, hyperglycemia directly causes NOX2 activation and ensuing inflammation. This discovery shows NOX2 as an intriguing therapeutic target worth pursuing and offers important new insights into the mechanisms underlying the progression of diabetes.
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