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IIT-Mandi researchers discover biochemical link between fatty liver disease and type 2 diabetes

Non-alcoholic fatty liver disease is often associated with type 2 diabetes, with nearly five crore Indian adults suffering from both diseases.
New Delhi, September 6

Researchers at the Indian Institute of Technology (IIT), Mandi, have discovered a biochemical link between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes.

According to officials, the findings of the research published in the “Journal Diabetes” also offer new therapeutic pathways to control or even reverse fatty liver-induced diabetes.

NAFLD is often associated with type 2 diabetes, with nearly five crore Indian adults suffering from both diseases.

“NAFLD is an independent predictor of insulin resistance and type 2 diabetes mellitus (T2DM). 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 Prosenjit Mondal, Associate Professor, IIT-Mandi.

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 the existing T2DM. At a biochemical level, S100A6 was found to inhibit insulin secretion by activating the Receptor for Advanced Glycation End (RAGE) product on pancreatic beta cells,” Mondal said.

Surbhi Dogra, a research scholar at IIT-Mandi, explained that another observation from the research was that the depletion of S100A6 improves insulin secretion and the regulation of blood glucose in mice, which suggests that S100A6 contributes to the pathophysiology of diabetes in NAFLD.

“At a scientific level, the research presents the molecular and cellular events associated with S100A6 secretion in fatty liver, and its adverse impact on beta-cell insulin release. From a practical, diagnostic angle, it shows that elevated levels of S100A6 in the blood may serve as a biomarker to identify risks of T2DM among NAFLD patients.

“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 is now understood, the use of RAGE antagonistic molecules can restore the functions of beta cells in NAFLD patients,” Dogra said.

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