Gluconeogenesis and oxidative stress in renal proximal tubular cells

Abstract

This thesis explores the hypothesis that renal gluconeogenesis has a protective role against oxidative stress in proximal tubular cells. Oxidative stress is a primary driver of pathophysiology in many diseases. This thesis reviews the fundamental factors that drive oxidative stress through electron leakage in mitochondria, highlighting tissue metabolic rate and tissue oxygenation as important driving factors. The proximal tubules of the kidneys are emphasized as being highly exposed to these driving factors, making them predisposed for electron leakage and therefore reliant on mitigation of oxidative stress through antioxidative defenses. It is known that glycolysis supports antioxidative systems, but proximal tubular cells run gluconeogenesis instead of glycolysis and a possible role of gluconeogenesis in protecting against oxidative stress has not received attention. This thesis employs a non systematic literature review to explore a hypothesis involving several interconnected topics, attempting to synthesize existing knowledge to inform the generation of new ideas, testable hypotheses and future experiments. The primary result of this review is the finding that there is conceptual support for the hypothesis and that it has some plausibility, encouraging further exploration. However, several topics have been omitted due to scope limitations that could be important for the hypothesis in question. Possible interpretations and future directions are discussed.