New York, April 9:
A team of researchers, including an Indian-origin scientist, has identified key inflammatory mechanisms underlying Type 1 diabetes and obesity-related kidney dysfunction.
Diabetic kidney disease is the leading cause of end-stage kidney disease and is a major risk factor for cardiovascular disease.
The findings showed that an increase in amounts of Sphingomyelin — a type of fatty acid commonly found in cell membranes and nervous tissue — has the potential to trigger the inflammatory mechanisms that can damage functioning of kidneys.
Sphingomyelin has been known to drive an increase in the ratio of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) — molecules involved in intracellular energy transfer in kidneys — in glomerular cells of the kidney in mice with diabetes, obesity or both.
Diabetes and obesity leads to an increase in the ATP levels and decreases the AMP levels, disrupting the balance leading to the dysfunctioning of the kidneys.
“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,” said Sharma, professor at the University of California San Diego in the US.
The team analysed the kidneys of experimental mice with Type 1 diabetes and mice fed on a high-fat diet.
The results also showed that deficiency in the production of insulin in the body or the resistance to externally induced insulin leads to an increase in amounts of sphingomyelin.
“We found that insulin deficiency and insulin resistance, two hallmarks of diabetes, seem to be associated with increased sphingomyelin in the kidney, which trigger damaging inflammatory mechanisms,” Sharma noted in the paper published online in the journal EbioMedicine.
The insights could have major impact on developing new biomarkers and novel therapeutics for diabetic and obesity-related kidney diseases.
“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 concluded.