Discovery of protein function ‘important step’ in diabetes treatment

Morgan Liotta

4/09/2020 3:03:33 PM

The protein has been shown to decrease blood glucose levels – showing strong potential to be used as a basis for longer term treatment.

Close up of blood glucose monitoring machine
Some diabetes medication treatments may have ‘limited tolerability’.

Current estimates show that around 1.7 million Australians have diabetes and 280 Australians will develop diabetes every day. Type 2 diabetes represents 85–90% of all cases of diabetes.
And those cases are growing.
Dr Gary Deed, Chair of the RACGP Specific Interests Diabetes network recently expressed concern that people with diabetes may be delaying or avoiding regular care during the COVID-19 pandemic – a timely reminder given diabetes has been linked with poor prognosis in people with COVID-19.
However, Australian and international researchers have made a world-first discovery that may address these concerns.
The research, published in Science Translational Medicine, found that the sparc-related modular calcium-binding protein 1 (SMOC1), naturally produced by the liver, was found to improve blood sugar levels in animal models with diabetes – thus holding the potential to decrease blood glucose levels in humans with newly diagnosed and advanced type 2 diabetes.
It is anticipated that an engineered long-lasting form of SMOC1 could potentially be used as a more effective long-term treatment for people with type 2 diabetes. 
‘Inter-tissue communication is a fundamental feature of metabolic regulation, and the liver is central to this process,’ the authors wrote. ‘We have identified SMOC1 as a glucose-responsive hepatokine and regulator of glucose homeostasis.’
Acknowledging that current treatments such as metformin are effective but may have ‘limited tolerability’ and ‘significant side effects’, the authors concluded that SMOC1 is more effective at improving blood glucose control, and reducing fatty liver and blood cholesterol levels. 
Such findings verify SMOC1 as a potential pharmacological target for the management of glycaemic control in type 2 diabetes.
‘This study is an early but important step to exploring options to manage type 2 diabetes, as emerging numbers are such a burden to healthcare worldwide,’ Dr Deed told newsGP.
‘Australian research such as this needs ongoing support as the quality of research here is world-leading.
‘[In the interim], if GPs need an update on current management options for their patients, refer to the RACGP’s Diabetes Handbook resource.’
Dr Magdalene Montgomery, lead author of the study, said increased incidence of type 2 diabetes meant treatments such as the new class of SMOC1-based treatments are ‘urgently needed’ to manage high blood glucose levels and reduce the risk of developing other chronic conditions.
‘Any therapy that can effectively reduce blood glucose levels can have an enormous impact on patients,’ Dr Montgomery said.
‘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.’ 
Diabetes medications that can be used alone or in combination to help maintain blood glucose levels have either limited effectiveness or off-target effects that adversely affect the patient’s health, and the discovery of the protein’s role is an important development to new approaches in this area, according to the research.
The next step is implementation of human trials, which would require engagement from primary care and the pharmaceutical industry.
It is hoped the new SMOC1-based treatment will be unique among known type 2 diabetes medications, but it is unlikely to be effective for people with type 1 diabetes who have insulin deficiency.
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