An in vitro type 2 diabetic cell model demonstrated significantly increased PLIN1 and PPARγ expression (p<0.05) and decreased ATP production genes compared to healthy cells.
In an in vitro model, diabetic conditions alter the expression of PPAR pathway regulators and downregulate mitochondrial ATP production genes, suggesting a mechanism for diabetic cardiomyopathy in chronic kidney disease.
p-value: p=<0.05
Background: Diabetes is a major risk factor for both cardiovascular disease (CVD) and chronic kidney disease (CKD), bringing a growing public health threat. Our previous studies identified deficiencies in heat shock proteins and translocase of the inner mitochondrial membrane (TIM) proteins as contributors to the development of hypertensive and uremic cardiomyopathy. In this work, we extend these findings by examining the mechanisms by which mitochondrial dysfunction contributes to CVD and diabetic cardiomyopathy in the context of CKD. Methods: Commercially available primary human atrial and ventricular cardiac myofibroblast cells and primary human aortic endothelial cells from three different age-matched sources were used in our type 2 diabetic cell model, in vitro. Immunohistochemistry, western blotting, Next Generation RNA Sequencing, and real-time polymerase chain reaction (qPCR) were used in our proposed study. Results: In our study, we examined the key PPAR pathway regulator, Perilipin 1 (PLIN1), and PPARγ, which were significantly (p< 0.05) increased in our in vitro diabetic cell model. Furthermore, the PPARγ inhibitor FABP4 (fatty acid binding protein-4), which functions as an atherosclerosis promoter, was significantly up-regulated (p< 0.05) in the non-diabetic cardiac myofibroblast and aortic endothelial cells. Additionally, our data indicate that ATP5F1E (ATP synthase F1 subunit epsilon) and the cAMP-regulating enzyme phosphodiesterase 8B are significantly increased (p< 0.01) in normal cardiac myofibroblasts and aortic endothelial cells. Moreover, major ATP production genes—OPA1, MFN1, and TIM—are significantly upregulated (p< 0.05) in healthy cells. Conclusion: Mitochondrial ATP synthesis is the primary energy source for intracellular metabolic pathways, and our study shows that mitochondrial dysfunction and downregulation of ATP production may inhibit the hydrolysis of the second messenger cAMP that promotes the development of CVD and diabetic cardiomyopathy in CKD. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Lu et al. (Fri,) conducted a other in Diabetic cardiomyopathy in chronic kidney disease. In vitro type 2 diabetic cell model vs. Non-diabetic/healthy cells was evaluated on Expression of PPAR pathway regulators and ATP production genes (p=<0.05). An in vitro type 2 diabetic cell model demonstrated significantly increased PLIN1 and PPARγ expression (p<0.05) and decreased ATP production genes compared to healthy cells.