Scientists crack insulin mystery, may see end of needles

January 11, 2013

Melbourne, Jan 11: In a major breakthrough that could help millions of diabetics, Australian researchers have solved a 20-year mystery that could which could spell the end of daily injections.

The new knowledge on how insulin works at a molecular level could be exploited to develop improved insulin medications to treat both type 1 and type 2 diabetes, they said.

Researchers from the Walter and Eliza Hall Institute of Medical Research have captured the first three-dimensional images of insulin "docking" to its receptor, a mystery scientists have been trying to solve for two decades.

Previously, scientists remained unsure as to how insulin binds to the receptor on the surface of cells to allow them to take up sugar from the blood and transform it into energy.

The international research team was led by scientists from the Walter and Eliza Hall Institute (WEHI) in Melbourne, with collaborators from La Trobe University, the University of Melbourne, Case Western Reserve University, the University of Chicago, the University of York and the Institute of Organic Chemistry and Biochemistry in Prague.

Lead researcher Mike Lawrence, an Associate Professor at the institute's Structural Biology division said: "This discovery could conceivably lead to new types of insulin that could be given in ways other than injection, or an insulin that has improved properties or longer activity so that it doesn't need to be taken as often. It may also have ramifications for diabetes treatment in developing nations, by creating insulin that is more stable and less likely to degrade when not kept cold, an angle being pursued by our collaborators. Our findings are a new platform for developing these kinds of medications,"

Lawrence said the insulin is a key treatment for diabetics, but there are many ways that its properties could potentially be improved, the Gizmag website reported.

"Understanding how insulin interacts with the insulin receptor is fundamental to the development of novel insulins for the treatment of diabetes. Until now we have not been able to see how these molecules interact with cells. We can now exploit this knowledge to design new insulin medications with improved properties, which is very exciting," he said.

The Assoc professor said the team was excited to reveal for the first time a three-dimensional view of insulin bound to its receptor.

The study was published in the journal Nature on January 9.

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Agencies
January 26,2020

High-protein diets may help people lose weight and build muscle, but there is a downside to it --a greater heart attack risk. Researchers now report that high-protein diets boost artery-clogging plaque.

The research in mice showed that high-protein diets spur unstable plaque -- the kind most prone to rupturing and causing blocked arteries.

More plaque buildup in the arteries, particularly if it's unstable, increases the risk of heart attack.

"There are clear weight-loss benefits to high-protein diets, which has boosted their popularity in recent years," said senior author Babak Razani, associate professor at Washington University School of Medicine in St. Louis, Missouri.

"But animal studies and some large epidemiological studies in people have linked high dietary protein to cardiovascular problems. We decided to take a look at whether there is truly a causal link between high dietary protein and poorer cardiovascular health," Razani added.

The researchers studied mice who were fed a high-fat diet to deliberately induce atherosclerosis, or plaque buildup in the arteries.

Some of the mice received a high-fat diet that was also high in protein. And others were fed a high-fat, low-protein diet for comparison.

The mice on the high-fat, high-protein diet developed worse atherosclerosis -- about 30 per cent more plaque in the arteries -- than mice on the high-fat, normal-protein diet, despite the fact that the mice eating more protein did not gain weight, unlike the mice on the high-fat, normal-protein diet.

"A couple of a scoop of protein powder in a milkshake or smoothie adds something like 40 grams of protein -- almost equivalent to the daily recommended intake," Razani said.

"To see if protein has an effect on cardiovascular health, we tripled the amount of protein that the mice receive in the high-fat, high-protein diet -- keeping the fat constant. Protein went from 15 per cent to 46 per cent of calories for these mice".

Plaque contains a mix of fat, cholesterol, calcium deposits and dead cells. Past work by Razani's team and other groups has shown that immune cells called macrophages work to clean up plaque in the arteries.

But the environment inside plaque can overwhelm these cells, and when such cells die, they make the problem worse, contributing to plaque buildup and increasing plaque complexity.

"In mice on the high-protein diet, their plaques were a macrophage graveyard," Razani informed.

To understand how high dietary protein might increase plaque complexity, Razani and his colleagues also studied the path protein takes after it has been digested -- broken down into its original building blocks, called amino acids.

"This study is not the first to show a telltale increase in plaque with high-protein diets, but it offers a deeper understanding of the impact of high protein with the detailed analysis of the plaques," said Razani.

"This work not only defines the critical processes underlying the cardiovascular risks of dietary protein but also lays the groundwork for targeting these pathways in treating heart disease," he added.

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Agencies
June 27,2020

After admitting that the world may have a COVID-19 vaccine within one year or even a few months earlier, the World Health Organisation (WHO) on Friday said that UK-based AstraZeneca is leading the vaccine race while US-based pharmaceutical major Moderna is not far behind.

WHO Chief Scientist Soumya Swaminathan stated that the AstraZeneca's coronavirus vaccine candidate is the most advanced vaccine currently in terms of development.

"I think AstraZeneca certainly has a more global scope at the moment in terms of where they are doing and planning their vaccine trials," she told the media.

AstraZeneca's Covid-19 vaccine candidate developed by researchers from the Oxford University will likely provide protection against the disease for one year, the British drug maker's CEO told Belgian radio station Bel RTL this month.

The Oxford University last month announced the start of a Phase II/III UK trial of the vaccine, named AZD1222 (formerly known as ChAdOx1 nCoV-19), in about 10,000 adult volunteers. Other late-stage trials are due to begin in a number of countries.

Last week, Swaminathan had said that nearly 2 billion doses of the COVID-19 vaccine would be ready by the end of next year.

Addressing the media from Geneva, she said that "at the moment, we do not have a proven vaccine but if we are lucky, there will be one or two successful candidates before the end of this year" and 2 billion doses by the end of next year.

Scientists predict that the world may have a COVID-19 vaccine within one year or even a few months earlier, said the Director-General of the World Health Organization even as he underlined the importance of global cooperation to develop, manufacture and distribute the vaccines.

However, making the vaccine available and distributing it to all will be a challenge and will require political will, WHO chief Tedros Adhanom Ghebreyesus said on Thursday during a meeting with the European Parliament's Committee for Environment, Public Health and Food Safety.

One option would be to give the vaccine only to those who are most vulnerable to the virus.

There are currently over 100 COVID-19 vaccine candidates in various stages of development.

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February 4,2020

Despite tremendous advances in treatment of congenital heart disease (CHD), a new global study shows that the chances for a child to survive a CHD diagnosis is significantly less in low-income countries.

The research revealed that nearly 12 million people are currently living with CHD globally, 18.7 per cent more than in 1990.

The findings, published in The Lancet, is drawn from the first comprehensive study of congenital heart disease across 195 countries, prepared using data from the Global Burden of Diseases, Injuries and Risk Factors Study 2017 (GBD).

"Previous congenital heart estimates came from few data sources, were geographically narrow and did not evaluate CHD throughout the life course," said the study authors from Children's National Hospital in the US.

This is the first time the GBD study data was used along with all available data sources and previous publications - making it the most comprehensive study on the congenital heart disease burden to date.

The study found a 34.5 per cent decline in deaths from congenital disease between 1990 to 2017. Nearly 70 per cent of deaths caused by CHD in 2017 (180,624) were in infants less than one year old.

Most CHD deaths occurred in countries within the low and low-middle socio-demographic index (SDI) quintiles.

Mortality rates get lower as a country's Socio-demographic Index (SDI) rises, the study said.

According to the researchers, birth prevalence of CHD was not related to a country's socio-demographic status, but overall prevalence was much lower in the poorest countries of the world.

This is because children in these countries do not have access to life saving surgical services, they added.

"In high income countries like the United States, we diagnose some heart conditions prenatally during the 20-week ultrasound," said Gerard Martin from Children's National Hospital who contributed to the study.

"For children born in middle- and low-income countries, these data draw stark attention to what we as cardiologists already knew from our own work in these countries -- the lack of diagnostic and treatment tools leads to lower survival rates for children born with CHD," said researcher Craig Sable.

"The UN has prioritised reduction of premature deaths from heart disease, but to meet the target of 'ending preventable deaths of newborns and children under 5 years of age,' health policy makers will need to develop specific accountability measures that address barriers and improve access to care and treatment," the authors wrote.

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