Research Targets Inflammatory Mechanisms in Diabetes, Kidney Dysfunction

Increased amounts of the fatty acid sphingomyelin were found in mice with type 1 diabetes and obesity-related kidney dysfunction.

A study published in EBioMedicine analyzed the kidneys of mice with type 1 diabetes and mice that were fed a high-fat diet.

Researchers found that both insulin resistance and insulin deficiency, 2 hallmarks of diabetes, seemed to be associated with an increase in sphingomyelin in the kidney. This increase triggers damaging inflammatory mechanisms.

Sphingomyelin is believed to be a driver for the increase of adenosine triphosphate (ATP) and adenosine monophosphate-activated protein (AMP) in glomerular cells of the kidney in the study mice.

ATP and AMP are involved in intracellular energy transfer, while glomerular plays a key role in cleansing the blood.

“ATP is involved in every cellular function. It is the energy currency of the cell,” said senior study author Kumar Sharma, MD. “But too much ATP causes inflammation. We believe that sphingomyelin fuels increases in ATP and decreases in AMP that result in inflammation which leads to cell dysfunction, fibrosis and endothelial damage underlying diabetic kidney disease.”

Normally, the ratios of ATP and AMP are tightly regulated, however, the mechanisms triggered by obesity and diabetes appear to disrupt this balance.

“Due to difficulties in the stability of ATP, it was uncertain whether there was increased ATP or decreased ATP production with diabetes,” Sharma said.

The findings could help in the future for the development of new biomarkers and novel therapeutics for diabetic- and obesity-related complications.

“It may be possible to create new treatments by blocking ATP and the inflammatory pathways consequent to that or by developing ways to reduce the amount or activity of sphingomyelin in the kidney,” Sharma said.