Type 2 diabetes mellitus induced autophagic response within pulmonary tissue in the rat model

Introduction: The current experiment aimed to address the impact of type 2 diabetes mellitus on autophagy status in the rat pulmonary tissue. Methods: In this study, 20 male Wistar rats were randomly allocated into two groups as follows: control and diabetic groups. To induce type 2 diabetes mellitus, rats received a combination of streptozotocin (STZ) and a high-fat diet. After confirmation of diabetic condition, rats were maintained for 8 weeks and euthanized for further analyses. The pathological changes were assessed using H&E staining. We also measured transforming growth factor-(3 (TGF-(3), bronchoalveolar lavage fluid (BALF), and tumor necrosis factor-alpha (TNF-alpha) in the lungs using ELISA and real-time PCR analyses, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were monitored in diabetic lungs to assess oxidative status. We also measured the expression of becline-1, LC3, and P62 to show autophagic response under diabetic conditions. Using immunofluorescence staining, protein levels of LC3 was also monitored. Results: H&E staining showed pathological changes in diabetic rats coincided with the increase of TNF-alpha (-1.4-fold) and TGF-(3 (-1.3-fold) compared to those in the normal rats (P < 0.05). The levels of MDA (5.6 +/- 0.4 versus 6.4 +/- 0.27 nM/mg protein) were increased while SOD (4.2 +/- 0.28 versus 3.8 +/- 0.13 U/mL) activity decreased in the diabetic rats (P < 0.05). Real-time polymerase chain reaction (PCR) analysis showed the up-regulation of Becline-1 (-1.35-fold) and LC3 (-2fold) and down-regulation of P62 (-0.8-fold) (P < 0.05), showing incomplete autophagic flux. We noted the increase of LC3+ cells in diabetic condition compared to that in the control samples. Conclusion: The prolonged diabetic condition could inhibit the normal activity of autophagy flux, thereby increasing pathological outcomes.

Automated summary

This study investigated the impact of type 2 diabetes mellitus on autophagy status in rat pulmonary tissue. The results showed that diabetes led to pathological changes in the lungs, accompanied by increased levels of TNF-alpha and TGF-beta. It also disrupted the oxidative status and inhibited the normal activity of autophagy flux.