A team of researchers from IIT Mandi on Tuesday said it has discovered a biochemical link between fatty liver disease and type 2 diabetes which allows newer techniques to diagnose and offer new therapeutic pathways for fatty liver-induced diabetes.
The prevalence of non-alcoholic fatty liver disease (NAFLD) in India is rapidly increasing and recent surveys show that 40 per cent of adults suffer from it, according to the team, adding that NAFLD is often associated with type 2 diabetes, with nearly 50 million adults having both diseases.
NAFLD is an independent predictor of insulin resistance and type 2 diabetes.
“However, how NAFLD affects the insulin-releasing pancreatic beta-cell function was not fully understood. We aimed at finding the relationship between beta-cells failure and the accumulation of liver fat produced from carbohydrates in a process called ‘de novo’ lipogenesis,” said Dr Prosenjit Mondal, associate professor, school of biosciences and bioengineering.
The findings were published in the Journal Diabetes.
The research team analysed blood samples extracted from fat-fed mice and human NAFLD patients. Both samples had high amounts of a calcium-binding protein termed ‘S100A6’ (this protein is released by the fatty liver and serves as a communication link between the liver and the pancreas).
‘S100A6’ adversely affects the insulin secretion ability of the beta-cells, thereby resulting in or exacerbating existing type 2 diabetes.
Biochemically, ‘S100A6’ was found to inhibit insulin secretion by activating the Receptor for Advanced Glycation End product (RAGE) on pancreatic beta-cells.
The study also presents the molecular and cellular events associated with ‘S100A6’ secretion in fatty liver, and its adverse impact on beta-cell insulin release.IIT researchers spot biochemical link between fatty liver disease, diabetes
However, at a therapeutic level, this study shows that removing the circulating S100A6 from blood can help in preserving beta-cell function.
Furthermore, since the biochemical pathway by which S100A6 acts can now be understood, the use of RAGE antagonistic molecules can restore the functions of beta-cells in NAFLD patients, the researchers said.
“Another important observation was that the depletion of ‘S100A6′ improves insulin secretion and the regulation of blood glucose in mice, which suggests that aS100A6’ contributes to the pathophysiology of diabetes in NAFLD,” said Surbhi Dogra from IIT Mandi.
