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Centenary Institute - Medical Research
Centenary Institute - Medical Research

Enzyme insight could lead to new diabetes treatment

Research led by the Centenary Institute has discovered that the lack of an enzyme in the liver called sphingosine kinase 2 (SphK2) results in pronounced insulin resistance and glucose intolerance, both symptoms of early stage type 2 diabetes.

The findings raises the possibility of a new treatment approach for diabetic patients whose glucose blood levels are dangerously high.

In the study, reported in the science journal ‘Proceedings of the National Academy of Sciences of the United States of America (PNAS), the researchers were able to demonstrate that the enzyme SphK2 was crucial to the blood glucose regulation process.

“Using mouse models, we found that a lack of SphK2 in the liver causes an accumulation of a fat product, sphingosine that, in turn, impairs insulin function in the liver,” said senior author of the study, Dr Yanfei (Jacob) Qi, Head of the Lipid Cell Biology Laboratory at the Centenary Institute.

It is insulin that signals to fat, liver and muscle cells to take-up glucose from the blood. Insulin resistance is when the cells do not respond to the insulin properly and fail to lower glucose levels adequately, potentially resulting in the development of Type 2 diabetes.

“Our study has been able to demonstrate that the enzyme SphK2 is a key player in the regulation of insulin. Future research can now look at targeting both SphK2 and sphingosine, by either genetic or pharmacological means. If we can help normalise their levels in the body we can then aid the management of both insulin resistance and diabetes,” said Dr Qi.

It is estimated that approximately 1.8 million Australians suffer from some form of diabetes  with the disease associated with a reduced life span, blindness, amputation, increased risk of heart disease as well as a poorer quality of life.

“Our findings are important as they may provide us with a completely new way to treat diabetes and to help change lives for the better,” said Dr Qi.

Publication: Regulation of hepatic insulin signaling and glucose homeostasis by sphingosine kinase 2.

Lift for Centenary Institute diabetes research

The official launch of the National Drug Discovery Centre (NDDC) has seen Centenary Institute researcher, Associate Professor Anthony Don, announced as one of the first recipients of Australian Government funding that will give him heavily subsidised access to the new Centre’s advanced drug screening facilities. The opportunity will fast-track Associate Professor Don’s research into treating type 2 diabetes.

Associate Professor Don, Head of the Lipid Metabolism and Neurochemistry Laboratory at Centenary is leading a project aimed at developing a new class of drugs targeting abnormal lipid (fat) metabolism to treat type 2 diabetes and obesity.

“My team leads internationally in the development of a new class of drugs targeting specific fat molecules called ceramides,” says Associate Professor Don.

“Drugs that block ceramide formation in the liver and fat tissue should help greatly with reducing weight gain and reversing the insulin resistance that causes type 2 diabetes,” he says.

The collaboration with the NDCC will allow Associate Professor Don to accelerate both his drug development program and related research activity.

Based at the Walter and Eliza Hall Institute of Medical Research, the NDDC provides robotic high-throughput drug screening. This is the process of using advanced automation to find a new drug against a chosen biological target for a particular disease.

The Australian Government is subsidising up to 90 per cent of standard screening costs offered by the new Centre to successful applicants–such as Associate Professor Don– through its Medical Research Future Fund.

Further information on Associate Professor Don and his research can be found here: https://www.centenary.org.au/cen_author/associate-professor-anthony-don/

Extra! Extra! Read all about it.

Dr Ka Ka Ting, a researcher within Centenary’s Vascular Biology Program, has had one of her images featured on the front cover of scientific journal Diabetologia.

Recently, Dr Ting led a study which found a novel drug (developed by Centenary scientists) could be used to effectively treat diabetic retinopathy; the main cause of blindness from diabetes.

This paper was also published in Diabetologia.

Congratulations Dr Ting on your wonderful success!

New treatment for diabetes-related blindness could be in sight

Pictured: Lead author and Centenary Institute researcher, Dr Ka Ka Ting using Centenary’s state-of-the-art confocal microscope.

Scientists at the Centenary Institute have developed a novel drug which could potentially be used to effectively treat patients with diabetic retinopathy; the main cause of blindness from diabetes.

The key process involved in diabetic retinopathy pathology is the breakdown of the blood-retinal barrier (BRB), which is normally impermeable. Its integrity relies on how well capillary endothelial cells are bound together by tight junctions. If the junctions are loose or damaged, the blood vessels can leak.

In collaboration with researchers in Denmark, scientists at the Centenary Institute in Sydney have demonstrated in mouse models, how a novel drug, CD5-2, can mend the damaged blood retinal barrier and reduce vascular leakage.

“With limited treatment options currently available, it is critical we develop alternative strategies for the treatment of this outcome of diabetes,” says lead author Dr Ka Ka Ting from the Centenary Institute.

Read the full media release.

See the original paper on Diabetologia.

A new way to target high rates of obesity

LISTEN: Associate Professor Anthony Don speaks to ABC RN Breakfast host Fran Kelly.

A novel drug is being touted as a major step forward in the battle against Australia’s escalating rates of obesity and associated metabolic diseases. As it stands, 2 in 3 adults in Australia are classified as being overweight or obese. A long-term study between researchers at the Centenary Institute and UNSW Sydney has led to the creation of a drug which targets an enzyme linked to insulin resistance – a key contributor of metabolic diseases, such as Type II diabetes.

The study has been published in the highly-regarded scientific journal Nature Communications. Surprisingly, although the drug was very effective at reducing the lipids of interest in skeletal muscle, it did not prevent mice (which had been fed a high-fat diet to induce metabolic disease) from developing insulin resistance. Instead, it prevented the mice from depositing and storing fat by increasing their ability to burn fat in skeletal muscle.

“From here, I would like to develop drugs which target both the Ceramide Synthase 1 and 6 enzymes together, and see whether it produces a much stronger anti-obesity and insulin sensitising response. Although these drugs need more work before they are suitable for use in the clinic, our work so far has been a very important step in that direction,” says Centenary Institute’s Associate Professor Anthony Don.

Centenary PhD student Ameline Lim must also be recognised for her role in conducting a significant amount of the laboratory work and data analysis throughout the project, which formed the basis for her PhD thesis.

Read the full media release.

(Pictured: Centenary’s Associate Professor Anthony Don)