Liver Protein Could Unlock New Type 2 Diabetes Treatment: Study
Thu, April 22, 2021

Liver Protein Could Unlock New Type 2 Diabetes Treatment: Study


The function of protein was recently discovered associated with diabetes. It could lower the levels of glucose better compared to the first-line medication.

The function discovery of a protein linked to type 2 diabetes was led by researchers at the University of Melbourne, an Australian public research university. The protein called SMOC1 was not new in medical science, but its function was unknown. The discovery unveiled its capability to lower blood sugar during spikes. The study showed its performance far greater than metformin, the first-line medication for type 2 diabetes. They published their findings in the journal Science Translational Medicine.

What is Type 2 Diabetes?

Studies on diabetes showed that the metabolic disorder has two main types: type 1 and type 2. While both exhibit issues on a hormone called insulin, they vary in terms of production and response. People with type 1 diabetes either cannot produce insulin or produce too little. Its main cause is often related to autoimmunity, wherein the immune system attacks the insulin-producing beta cells called islets of Langerhans. These cells are limited in numbers and can easily be terminated by immune cells.

Type 2 diabetes, on the other hand, is characterized by insensitivity to insulin. A person with type 2 can produce insulin normally but their body does not properly respond to the hormone. Thus, their blood sugar remains high even if their pancreas secrete insulin. Between the type 1 and type 2, the former is considered more dangerous due to insulin insufficiency, however, both types can lead to serious health complications.



According to the US Centers for Disease Control and Prevention, a federal agency, an estimated 10.2% of the US population were diagnosed with diabetes. Though, approximately 2.8% of the population were undiagnosed with the disease. The overall estimated diabetes prevalence across the country was 13% from 2013 to 2016. Between genders, 10% of the male population and 9.5% of the female population were diagnosed with diabetes.

By adult age group, 3% of aged 18 to 44 years, 13.8% of aged 45 to 64 years, and 21.4% of aged 65 and older were diagnosed with diabetes. By race, 9.4% of non-Hispanic Whites, 13.3% of non-Hispanic Blacks, 11.2% of non-Hispanic Asians, and 10.3% of Hispanics were diagnosed with diabetes.

Meanwhile, the German portal for statistics Statista showed the prevalence of type 2 diabetes among children and young people in England and Wales, between 2018 and 2019. A total of seven males and 12 females aged six to nine years, 81 males and 230 females aged 10 to 14 years, 155 males and 296 females aged 15 to 17 years, and 16 males and 38 females aged 18 to 19 years were diagnosed with type 2 diabetes.



Liver Protein Could Open Path to Better Diabetes Therapies

At the University of Melbourne, researchers finally uncovered a function of a liver protein. The function showed a link to glucose management, which could unlock future therapies for type 2 diabetes. These potential therapies might prevent diabetes-related complications, such as cardiovascular disease and kidney damage. This protein even had better glucose regulation compared to a popular first-line diabetes medication.

"Any therapy that can effectively reduce blood glucose levels can have an enormous impact on patients. 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," said Dr. Magdalene Montgomery, the lead author of the study and senior research fellow at the university.

The protein rediscovered in their study is the SMOC1. It is naturally secreted by the liver for a specific situation: when blood sugar goes up. In real-life, several minutes after a person eats a meal, glucose in the bloodstream begins to rise. After an hour, the increase in glucose will reach its peak. Aside from the pancreas, the liver participates in regulating glucose by releasing SMOC1. It helps insulin in mitigating the surge of sugar in the blood, avoiding dangers to other organs during the metabolism of nutrients.

Current treatments can be effective though issues like side effects and tolerability are known. The SMOC1 protein may lead science to a new class of diabetes drugs with greater effectiveness and fewer side effects. But synthetic creation of this protein needs many testing for safety and efficacy in preclinical and human clinical trials.

Researchers developed an engineered version of SMOC1. They used animal models modified to mimic diabetes symptoms. Next, they administered the synthetic drug into the animals. Results showed that the engineered version worked in lowering glucose of animals with diabetes. Then, they compared SMOC1's performance to the drug metformin. Both could reduce glucose levels but the protein exhibited some edges. SMOC1 could even lower liver and blood cholesterol levels – two distinct health issues experienced by many type 2 diabetes patients.

Further analysis of SMOC1 revealed its ability to enhance glucose metabolism of liver cells. This expressed possibility of synthetic SMOC1 compatible for in-human use. If a drug based on SMOC1 was developed, it could significantly improve the beneficial effects from combined healthy lifestyle and treatment on type 2 diabetes. However, researchers confirmed a drawback in their research. The protein would not benefit patients with type 1 diabetes.

Professor Matthew Watt, the senior author of the study, explained that the relevance of SMOC1 in glucose management depends on insulin production. Because type 1 diabetes cripples insulin production, SMOC1 alone could not effectively regulate glucose levels. In other words, the role of SMOC1 could only augment the function of insulin. Even if type 2 diabetes patients failed to respond properly to insulin, the liver protein would mitigate some of the consequences of that insensitivity. Thus, SMOC1 drugs would remain as treatment, not a cure for type 2 diabetes.

The research team is now planning for human clinical trials. They are engaging with the pharmaceutical industry to get support for these trials. If a deal is reached, SMOC1-based drugs may be tested for newly diagnosed, early, and advanced type 2 diabetes.