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Recurrent Hypoglycemia and Platelet Mitochondrial Dysfunction
Location: 53
Mentor: Dr. Kunjan Dave
Diabetes mellitus (DM) is a chronic metabolic disorder linked to numerous complications, including increased stroke risk and cardiovascular disease. Recurrent hypoglycemia (RH) is a common side effect of insulin therapy, and evidence suggests it may exacerbate stroke risk by activating platelets to promote thrombus formation. Platelet activation, particularly via mitochondrial dysfunction, plays a critical role in thrombogenesis. This project aims to investigate the impact of RH exposure on platelet mitochondrial function in insulin-treated diabetic (ITD) rats, modeling the diabetic and hypoglycemic states. We hypothesized that RH exposure induces mitochondrial dysfunction in platelets, leading to increased platelet activation and a heightened risk of ischemic stroke. To test this, diabetes will be induced in Wistar rats via streptozotocin (STZ) and treated with insulin pellets to replicate insulin therapy. Two experimental groups were established: ITD + RH, which will undergo recurrent hypoglycemia, and ITD + RH + Glucose, serving as a normoglycemic control group. Platelet mitochondrial function will be assessed by measuring oxygen consumption rates using various respiratory substrates and inhibitors. Additionally, mitochondrial complex activities will be measured spectrophotometrically. This project will provide valuable insight into the cellular mechanisms underlying the increased cardiovascular risk associated with recurrent hypoglycemia in diabetes management.
