Innovative drug could improve type 2 diabetes treatment – Medicine, Nursing and Health Sciences – Monash University

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+61 3 9903 0026 19 August 2022

A new drug that reboots how fat cells use insulin could revolutionise type 2 diabetes treatment and improve the outlook of hundreds of millions of patients globally.

A new drug that reboots how fat cells use insulin could revolutionise type 2 diabetes treatment and improve the outlook of hundreds of millions of patients globally.

The drug, called PATAS, is in development after a team of international researchers, including Monash University, decoded what causes insulin resistance in fat tissue cells. This has been a major stumbling block in treating and preventing type 2 diabetes.

PATAS, which is being developed by AdipoPharma, could be delivered by simple injection and possibly a patch. It may also have the potential to prevent type 2 diabetes, a major global epidemic, largely driven by obesity.

Type 2 diabetes involves high blood sugar levels and is caused by the resistance of body cells such as fat cells (adipocytes) to the action of insulin, the hormone that enables glucose to be properly utilised in the adipocytes and in the rest of the body.

Published in the American Diabetes Association journal Diabetes, the French, UK, USA and Australian teams research found an inability by fat cells to regulate metabolism using glucose causes insulin resistance.

The research was led by Inserm, Frances National Institute of Health and Medical Research, in collaboration with Monash University and the University of Birmingham (UK).

Dr Vincent Marion, the Inserm study coordinator and deputy director at the Laboratory of Medical Genetics in Strasbourg, France, along with his team, designed the breakthrough peptide drug PATAS and has shown that it was able to fix this problem by enabling glucose to be used in fat cells.

Co-researcher Paul Zimmet AO, Professor of Diabetes at Monash University, said the discovery could improve metabolic control of diabetes and reduce the risk of the serious complications of diabetes including heart, kidney, liver and eye disease.

PATAS corrects an abnormality in fat cells by separating two proteins, ALMS1 and PKC alpha, that are associated with insulin resistance by blocking insulin from initiating glucose uptake.

In rodent studies, PATAS reduced the insulin resistance, glucose intolerance and fat build up in the liver (steatosis). Beneficial effects were also observed in glucose intolerant animal models. Similarly, when used on cultured human fat cells in the laboratory and independent contract research organisations, the drug reactivated glucose uptake in the fat cells.

Professor Zimmet said the discovery was potentially one of the most important he had seen in his 45 years of diabetes research. Human clinical trials are likely to start in 2023.

This is a very exciting discovery that could have enormous health benefits, not just for people with type 2 diabetes, but also for patients with other chronic medical disorders caused by insulin resistance including cardiac diseases, and fatty liver and the Metabolic Syndrome, Professor Zimmet said.

Current drugs for type 2 diabetes mainly focus on lowering the high blood sugar level rather than targeting insulin resistance, the underlying cause.

This research study has for the first time, identified the root cause of insulin resistance in adipocytes, a precursor of type 2 diabetes, and developed a drug that reduces insulin resistance and restores normal glucose uptake.

Type 2 diabetes is very costly for global economies and diagnoses are rising and patients are becoming younger, with the disease now frequently detected in adolescents and children.

Diabetes affects 537 million people worldwide, most of whom have type 2 diabetes. The International Diabetes Federation says the annual global cost of diabetes treatment was USD$966 billion in 2021 up more than 300 per cent in the past 15 years.

This diabetes breakthrough emerged following research into Alstrom Syndrome, an ultra-rare genetic disease in children. It is associated with obesity and severe insulin resistance that leads to type 2 diabetes and an accelerated form of liver steatosis and fibrosis. The researchers found that insulin resistance was linked to the dysfunctional protein, ALMS1.

Building on this previous research, the multinational team next discovered that in normal fat cells and upon insulin signalling, a protein called PKC alpha is released from ALMS1 to trigger glucose uptake. With insulin resistance, PKC alpha is no longer released from ALMS1 and hence glucose is no longer absorbed by the fat cells to be utilised.

Dr Marion said that in cultured human adipocytes as well as in most relevant animal models, PATAS was able to separate the proteins and restore normal function of glucose uptake and utilisation in the fat cells.

Thanks to PATAS, which rescues the adipocytes (fat cells) that could no longer access glucose, they were once again able to take up glucose and metabolise it to synthesise and secrete healthy lipid metabolites which are beneficial to the entire body for maintaining insulin sensitivity and overall metabolic health, he said.

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Innovative drug could improve type 2 diabetes treatment - Medicine, Nursing and Health Sciences - Monash University