# Role of lactate dehydrogenase A in the regulation of podocyte metabolism and glucose uptake under hyperglycemic conditions

## TL;DR

This study explores how lactate dehydrogenase A (LDHA) affects podocyte metabolism and glucose uptake in diabetic conditions, revealing its role in kidney disease.

## Contribution

The study identifies LDHA as a key regulator of podocyte metabolism under hyperglycemia, offering new therapeutic insights for diabetic kidney disease.

## Key findings

- Hyperglycemia reduces LDHA expression and activity in podocytes.
- Lower LDH activity leads to metabolic disturbances and reduced glucose uptake.
- Reduced LDHA expression correlates with podocyte foot process loss.

## Abstract

Lactate is a cellular product of glycolytic metabolism, serving as both an additional oxidative energy substrate and a signaling molecule in metabolic regulation. Plasma lactate levels are elevated in diabetes, and chronic extracellular lactic acidosis is recognized as a negative prognostic marker for the disease. The development of diabetic kidney disease is closely associated with podocyte injury, which forms a crucial layer of the glomerular filtration barrier. Given that high extracellular glucose concentrations also induce lactate production and excretion in podocytes, we hypothesize that an appropriate LDH expression pattern is crucial for maintaining proper podocyte metabolism and function. Our research shows that hyperglycemia significantly decreases lactate dehydrogenase activity in podocytes. Specifically, reduced LDHA expression under hyperglycemic conditions contributes to metabolic disturbances in these cells. Lower LDH activity results in decreased glycolytic activity, altered expression of monocarboxylate transporters, reduced insulin-dependent glucose uptake, and a decrease in the number of podocyte foot processes. These findings underscore the essential role of LDHA in the metabolic adaptation of podocytes to elevated glucose levels typical of diabetes. By elucidating the molecular mechanisms underlying podocyte injury, our study provides new insights into potential therapeutic targets for preventing or mitigating diabetic kidney disease.

The online version contains supplementary material available at 10.1038/s41598-025-98797-0.