Liver protein could improve type 2 diabetes treatment
An international research team led by The University of Melbourne has found that the SMOC1 protein, which is naturally produced by the liver, can decrease blood glucose levels. An engineered form of SMOC1 could therefore potentially treat people with type 2 diabetes, the researchers wrote in the journal Science Translational Medicine.
Type 2 diabetes affects about one million Australian adults and 400 million people globally, with current treatments having limited tolerability and significant side effects. University of Melbourne Senior Research Fellow Dr Magdalene Montgomery said the increased incidence of type 2 diabetes means new treatments are urgently needed to manage the resultant high blood glucose levels.
“Any therapy that can effectively reduce blood glucose levels can have an enormous impact on patients,” said Dr Montgomery, who served as lead author on the new study.
“It lowers their risk of developing diseases such as cardiovascular disease; chronic kidney disease; damage to blood vessels, which causes blindness; the risk of amputations; and nerve damage, which causes pain.”
The research team engineered a long-lasting form of SMOC1 that reduced blood glucose levels in diabetic animal models. As explained by Dr Montgomery, “We knew that SMOC1 existed but its role in regulating blood glucose was unknown.
“We discovered SMOC1 as a protein that was secreted by the liver when blood glucose levels are high, suggesting that SMOC1 might play a role in blood glucose control. This turned out to be true.
“It was more effective at improving blood glucose control than the current frontline medication called metformin. It also reduces fatty liver and blood cholesterol levels, which are common health problems in type 2 diabetes patients.”
Senior author and University of Melbourne Professor Matthew Watt noted that diet and lifestyle have limited effectiveness as a treatment for type 2 diabetes, while current medications also have issues.
“There are several medications that can be used alone or, increasingly, in combination, that help maintain blood glucose levels in patients,” Prof Watt said.
“However, all type 2 diabetes medications, without exception, have either limited effectiveness or off-target effects that adversely affect the patient’s health. We need to develop new approaches.”
He said the next step for the SMOC1 treatment will be human trials, which would require engagement from the pharmaceutical industry.
“We anticipate, based on animal studies, that SMOC1 would be effective in people with newly diagnosed and advanced type 2 diabetes,” Prof Watt said.
“Given the number of people with diabetes, the impact on reducing the burden on the healthcare system could be enormous, including less hospital visits and shorter hospital stays.
“We have also shown that SMOC1 improves glucose metabolism in human liver cells, so we are certainly optimistic that SMOC1 will be effective in humans.”
He said the new treatment is likely to require injection once a week, although the team is working on other methods.
“The injectable could move to human trials relatively quickly with the right support,” Prof Watt said. “The alternative approaches would be a long way off.”
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