New protein improves insulin sensitivity and blood glucose control

University of Melbourne researchers have identified a new protein which improves insulin sensitivity and blood glucose control.

University of Melbourne researchers have identified a new protein called Arylsulfatase A (ARSA), which improves insulin sensitivity and blood glucose control.

They also found that increasing ARSA – either in the liver through gene therapy, or in the blood through protein therapy (injections of ARSA protein) – may potentially be a viable strategy for the treatment of insulin resistance and type 2 diabetes.

The findings, determined in a series of animal tests, put School of Biomedical Sciences researchers closer to determining whether the protein can be used as a new treatment for type 2 diabetes.

Published in Nature Communications, the study led by Dr Magda Montgomery and Professor Matt Watt, who describe global changes in protein secretion in non-alcoholic steatohepatitis (NASH), a state of advanced liver disease characterized by lipid accumulation and inflammation, and identifies ARSA as a regulator of liver to muscle communication – and as a potential therapeutic target for type 2 diabetes.

“Fat accumulation in the liver, known as non-alcoholic fatty liver disease (NAFLD), affects around 25 per cent of the global population, which means every fourth person has some form of NAFLD. If you are obese or have type 2 diabetes, your chance of having fatty liver increases to 50 to 80 per cent. The problem is, fatty liver can progress to more advanced liver disease, including NASH, liver fibrosis, cirrhosis and liver cancer,” Dr Montgomery said.

“Proteins secreted from the liver impact many other tissues, including your muscles, heart and brain in both positive and negative ways, and investigating protein secretion in various disease states will increase our understanding of metabolic regulation on a whole-body level.”

Dr Montgomery and Professor Watt’s research showed that the ARSA protein is important for inhibiting the release of specific lipids from the liver called lysophospholipids, and, thereby, for reducing blood levels of these lipids, which can be detrimental and induce insulin resistance on a systemic level.

ARSA protein and gene therapy has previously been shown to be a safe therapeutic approach for metachromatic leukodystrophy in humans, and future studies are warranted to assess the potential for ARSA as a therapeutic strategy for the treatment of type 2 diabetes.

To advance towards therapeutic development, more pre-clinical studies are needed, including further validation of the longer-term impact of increased ARSA in the liver and blood.

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