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Health News

Towards a New Drug Class in the Treatment of Type 2 Diabetes

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Towards a New Drug Class in the Treatment of Type 2 Diabetes 

Type 2 diabetes is a major public health problem that affects millions of people worldwide. Developing new drugs to help better treat its underlying causes is therefore a research priority.

In a new study coordinated by Inserm researcher Vincent Marion in collaboration with Monash University, the University of Birmingham (UK), and Alexander Fleming, former senior endocrinologist at the US Food and Drug Administration (FDA), the scientists have developed PATAS, a peptide that is part of a new class of antidiabetic drugs. PATAS can correct the metabolic abnormalities leading to type 2 diabetes and its associated comorbidities which include insulin resistance(1).

PATAS works by specifically targeting the adipocytes (fat cells) (2), restoring glucose entry and thus correcting and re-establishing the metabolic physiology of the adipose tissue. The teams hope to set up a clinical trial soon to test this new therapy. Their study has been published in the journal Diabetes.

Diabetes mellitus is a chronic condition that affects 537 million people worldwide, with the majority affected by type 2 diabetes. The prevalence of type 2 diabetes, which is characterized by high levels of glucose in the blood (see box), has been increasing for decades due to population aging, inactivity, and poor diet. The age of onset is also decreasing, and although the disease is considered to be an “adult disease”, it is now seen frequently in adolescents and children.

Available drugs treat the consequences of type 2 diabetes by focusing mainly on lowering blood glucose; they do not target the underlying biological mechanism that causes the disease. Despite the urgency for developing new and more effective treatments, there have been no disruptive therapeutic innovations to reach market in over a decade.

And this is precisely the objective of the research led by Inserm researcher Vincent Marion and his team at the Medical Genetics Laboratory (Inserm/Université de Strasbourg). In a recent study in collaboration with the University of Birmingham and Monash University, the scientists have developed a product called PATAS in a new class of diabetes drugs called “Adipeutics” (for therapies that specifically target the adipocytes).

Their study, conducted on animal models, shows that this new therapy specifically restores glucose uptake in the adipocytes, resulting in the treatment of insulin resistance with beneficial effects on the whole body. This is made all the more promising by the fact that treating insulin resistance has the potential to address not only type 2 diabetes but a large array of serious medical conditions that result from this resistance.

 

Type 2 diabetes in brief 

Diabetes mellitus is characterized by excessive blood glucose levels over a prolonged period of time: this is known as hyperglycemia.

Hyperglycemia is caused by a reduced sensitivity of the cells, particularly those in the liver, muscle, and adipose tissue, to insulin. This is known as “insulin resistance.”

Insulin is a hormone produced by the pancreas whose role is to facilitate the entry of glucose into the body cells as their main source of energy.  To meet the increased demand for insulin caused by the cells’ resistance to this hormone, the pancreas produces even more insulin, depleting the body requirements. Insulin production then becomes insufficient and the blood glucose levels rise as a result.

The role of adipocytes 

This study follows on from years of rigorous, in depth work carried out in the lab. In previous research, published in Diabetes in 2020, the scientists had identified a new therapeutic target for type 2 diabetes when investigating at an ultra-rare monogenic disease known as Alström syndrome.

The scientists had shown that adipose tissue abnormalities (3) caused by a dysfunctional protein called ALMS1 led to extremely severe insulin resistance associated with early-onset type 2 diabetes in people with Alström syndrome. In animal models, restoring the function of this protein within the adipocytes re-established blood glucose balance.

The teams then went on to focus more closely on ALMS1 and how it interacts with other proteins within the adipocytes. In particular, they have shown that in the absence of insulin, ALMS1 binds to another protein called PKC alpha. The activation of insulin in the adipocytes induces the separation of these two proteins ALMS1 and PKC alpha, resulting in glucose entry into cells. In people with diabetes, who are insulin-resistant, this link between the two proteins is maintained.

Drawing on this knowledge, the scientists have developed the peptide PATAS, which works by breaking the interaction between ALMS1 and PKC alpha – thus restoring insulin signaling in the adipocytes.

In mouse models of diabetes, PATAS has been able to re-establish the normal physiology of the adipocytes by restoring glucose uptake. “Thanks to PATAS, the adipocytes that could no longer access glucose were once again able to absorb it and then metabolize it in order to synthesize and secrete lipids which are beneficial to the entire body. These positive effects are visible in our animal models, with a marked improvement in insulin resistance. Other parameters and comorbidities are also improved, including better blood glucose control and decreased liver fibrosis and steatosis,” explains Vincent Marion.

These promising results in animals have paved the way for the researchers to organise a clinical trial as soon as possible, in order to test PATAS in humans. The successful development of a new class of antidiabetic drugs could have significant implications for public health, not only to treat type 2 diabetes but also many other cardio-metabolic disorders in which dysfunctional adipocytes and insulin resistance are very problematic.

In order to create value from these findings and facilitate the organization of such a trial, Vincent Marion has founded the start-up AdipoPharma SAS.

 

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Health News

UNSW

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NSW Northern Rivers Breaking News

UNSW

If you’ve been to any supermarket recently, you would’ve noticed the shelf space dedicated to milk alternatives such as oat, soy, almond and rice is expanding. Though they’re not strictly speaking ‘milk’, these plant-based beverages are gaining favour among consumers looking for a dairy-free option in their coffee mugs and cereal bowls.

According to the Australian Bureau of Statistics, we’re now drinking about half a metric cup of milk alternatives per person every week. In the milk marketplace, consumption of the likes of soy and almond milk is increasing at the same rate dairy milk is falling.

Experts from UNSW Sydney say there are many reasons we’re leaving cow’s milk behind in favour of the plant-based kind, including health reasons, ethical choices and personal preferences.

LACTOSE INTOLERANCE AND MORE PRODUCTS AVAILABLE

Professor Johannes le CoutreSchool of Chemical EngineeringUNSW Engineering, says he’s not surprised by the expansion of the plant-based milk aisle. The food and health expert says in the first place, human bodies are not physiologically optimised to digest dairy milk.

“Food history is full of examples where we try to mimic animal products, so having plant-based milk is not an entirely new idea,” Prof. le Coutre says.

“Human adults are not necessarily the target consumers for cow’s milk in nature. It’s a product meant for babies, specifically for cow babies,” he says.

Many adults have an intolerance to lactose – the sugar in dairy – to some degree. If they drink cow’s milk or eat other dairy by-products, they can experience bloating, pain and diarrhoea. For those people, plant-based milk offers a lactose-free alternative.

“If someone has an intolerance to dairy, it is easier for their body to digest plant-based milk,” says nutritionist Dr Rebecca Reynolds, adjunct lecturer, School of Population HealthUNSW Medicine & Health. “While some regular milk has the lactose removed, many prefer the taste of plant-based milk.”

Researcher in consumer behaviour, Associate Professor Nitika GargSchool of MarketingUNSW Business School, says the quality and variety of plant-based milk available has improved in recent times.

“The taste is undoubtedly a key factor because consumers don’t want to feel they need to compromise on flavour,” A/Prof. Garg says. “Today, if you feel uncomfortable consuming dairy milk, there are a lot more alternatives in the market you can try that weren’t available 20 years ago.”

AN ETHICAL CHOICE FOR ANIMALS AND THE ENVIRONMENT

Many people are also switching up their milk of choice for ethical reasons. One concern is the treatment of livestock in the dairy milk production process.

“There is a movement of consumers who resent animal products – such as milk – because they are not necessarily associated with good animal welfare,” Prof. le Coutre says.

To produce milk, cows must give birth. If the calves are not needed as replacements for the milking herd, they are killed, often not humanely. More cows die per calorie of milk production than cattle for meat production.

A/Prof. Garg says some of the growth in plant-based milks can also be attributed to changing consumer perceptions about the sustainability of the dairy industry. There is growing awareness about the impact it is having on the climate and the environment.

Research suggests a dairy-free diet could be a more environmentally friendly option, and people can make significant moves for the environment by just reducing their dairy intake, Dr Reynolds says.

Some plant milks might be more planet friendly than others though. For example, it’s estimated that growing a single almond requires 12 litres of water. Still, almond milk uses less land and water than dairy milk and has lower greenhouse gas emissions.

“[But] there are challenges when it comes to plant-based products in that they usually destroy a lot of nutritional goodness and require a lot of resources just to mimic a product [milk] that isn’t intended for human consumption in the first place,” Prof. le Coutre says.

HEALTH BENEFITS AND CALORIC CONCERNS

Milk alternatives are also becoming an increasingly popular choice among health-conscious consumers. But what some consider to be a ‘healthier’ option is not always the case, Prof. le Coutre says.

So how does dairy milk stack up nutritionally against plant-based milk? While there is scepticism about the health impacts of dairy products, evidence suggests dairy benefits health.

“Overall, cow’s milk has a better nutritional profile than plant milks, with more protein and micronutrients like calcium,” Dr Reynolds says. “However, plant-based milks often have micronutrients added to them, can have less overall fat and saturated fat than dairy milk and more healthy plant phenol antioxidants.”

There’s a wide variety of plant-based milks in the market, like oat, almond and rice, with varying nutritional quality. Soy might be the strongest dairy-free plant alternative in terms of nutritional profile.

“Some have added refined sugar, which includes ingredients like ‘organic brown rice syrup’, which is less healthy than the natural sugar lactose that’s found in cow’s milk,” Dr Reynolds says. “This means that they can also be higher in high glycaemic index carbohydrates, which can increase blood glucose levels more than lactose. They also have added oils, which are not as healthy as say olive oil, and they’re not suitable as stand-alone milks for children.”

Dr Reynolds says if plant milk and other dairy substitutes are fortified – that is, have micronutrients like calcium added – there might not be a need to supplement in a diet. However, it’s estimated over 50 per cent of Australians aged 2 years and above don’t consume enough calcium and other micronutrients.

“Overall, plant-based diets are still strongly linked to good health,” Dr Reynolds says.

THE FUTURE OF PLANT-BASED MILK

With their rapid rise, A/Prof. Garg expects plant-based milk to become an even more dominant player in the milk market. Perhaps one day, it might even supplant dairy milk in popularity.

“Much of the growth to date appears to be consumer-driven, so I would expect the trend to continue to grow. As these brands continue to scale up their manufacturing and marketing efforts, there’s a huge opportunity for a true milk substitute to emerge and compete with dairy,” she says.

A/Prof. Garg says governments also have a chance to take advantage of the anticipated global demand in the industry.

“People are choosing plant-based milk more and more, and so it would make sense for governments to take advantage of the opportunity to support the production here in Australia,” she says. “It would also still be supporting the Australian agricultural industry, which is an important consideration for some consumers.”

In the short-term, A/Prof. Garg says switching to plant-based milk might not be realistic for everyone because of its high price point.

“We do have an issue with making products such as plant-based milk accessible for everyone. They are more expensive, and some consumers who might want to switch can’t, especially with the cost of living right now where every dollar counts,” A/Prof. Garg says. “It might be something governments need to explore, to help subsidise in the same way they subsidise the dairy industry.”

Prof. le Coutre says plant-based milk – and plant-based mimetics more generally – will continue to play a significant role in strengthening our global food system.

“Plant-based products, existing animal-based materials and, someday soon, cell-based and blended products improve our food choices,” Prof. le Coutre says. “As we expand our portfolio of products, it enriches the spectrum of offerings in the market to everybody’s benefit.”

“Overall, if you can afford it, buying a plant-based milk fortified with micronutrients like calcium and without added sugar can be a good way to use your consumer power to help the environment and climate change,” Dr Reynolds says.

 

 

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Health News

THE WHOLE TOOTH ABOUT COVID’S EFFECTS ON OUR ORAL HEALTH

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THE WHOLE TOOTH ABOUT COVID’S EFFECTS ON OUR ORAL HEALTH 1/8/22

For Dental Health Week (1-7 August), one of the key findings from the Australian Dental Association’s (ADA) annual Consumer Survey of 25,000 Aussies, is that one in three people postponed dental treatment in the last 12 months due to COVID-related concerns.

Of those that postponed, this included 23% of 18-24s rising to 41% of 65-74s, with more women than men putting it off across all age ranges.

Why the delay? The main reason for delaying, as cited by respondents, is that they felt that their dental problem was not urgent (26%), while 17% were concerned about catching COVID at the dental clinic or travelling to it, 16% reported not being in a financial position for dental care and 14% did not attend due to lockdowns or were unable to travel to the dental clinic.

Of those who delayed their dental consultations, 21% felt this adversely affected them, while 17% were unsure whether it did. Residents of Victoria, NSW and the ACT who experienced greater periods of lockdown, more commonly reported that their oral health was adversely affected.

“These statistics tell us a lot about where oral health is sitting for people during the Covid pandemic,” said Dr Mikaela Chinotti, the ADA’s Oral Health Promoter and Sydney dentist.

“With people losing their jobs or working reduced hours, dental care took on a lesser priority or was inaccessible during lockdowns for some families.

“That said though, with two thirds of people still getting treatments or attending for check-ups particularly in states less impacted by lockdowns, this is good news for the nation’s oral health because oral conditions left untreated can result in serious consequences including on the rest of the body.”

Delaying tactics: Of those who put off a visit, 42% were putting off a usual dental check-up, 26% were putting off checking a new problem, and 24% were delaying treating an existing problem.

A further 8% put off their appointment for ‘Another Reason’. Reasons for doing so (in order from most reported) included a referral from another health professional for a related medical condition such as teeth grinding, care for a minor injury, cosmetic concerns such as teeth whitening, adjustment or fitting of a dental device like braces and buying dental products like a mouthguard or whitening products.

The next dental visit: Fortunately many Aussies don’t plan to delay for too long: 54% planned to go in the next 1-3 months, 22% were going to book within 3-12 months and others were either waiting for the pandemic to ease, or to reach full vaccination status or were still unsure.

“Anecdotally we’ve heard from many ADA dentist members that with the stress of the pandemic there’s been an increase in cracked teeth, tooth sensitivity and/or pain associated with clenching or grinding of the teeth and an increase in discomfort from the jaw joint,” said Dr Chinotti.

“For those Aussies who delayed dental care due to the COVID pandemic, Dental Health Week is a great reminder that it’s time to show you teeth some love by taking them on a date to the dentist.

“When not at the dentist, Aussies can also find up-to-date and evidence-based oral health advice online in the form of short educational videos, articles and a multi-episode podcast on the ADA’s consumer-focused website: www.teeth.org.au.”

 

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Health News

New development for hormone-free male contraceptive pill

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NSW Northern Rivers Breaking News

New development for hormone-free male contraceptive pill

MONASH UNIVERSITY

EMBARGOED until FRIDAY JULY 29, 7:30 AEST

A new study led by a team of Monash researchers working to develop a male contraceptive pill has identified that stinging nettle leaf extract has the potential to block a protein that controls the movement of sperm.

The discovery is an incremental yet important advance for the research group, led by Dr Sab Ventura from the Monash Institute of Pharmaceutical Sciences, who have previously shown that male infertility could be genetically achieved by simultaneously deleting two proteins that trigger the transport of sperm – α1A-adrenoceptor and P2X1-purinoceptor – but without affecting the long-term viability of sperm or sexual and general health.

 

The study, published in PLOS ONE, identified that stinging nettle leaf extract contains a component that could orally inhibit one of the two proteins, P2X1-purinoceptor. Dr Ventura said that this is an exciting step forward to show that the teams’ biological mechanism for male contraception is orally viable.

“The primary aim of this research was to investigate the activity of a commercially available stinging nettle extract as an inhibitor of the P2X1-purinoceptor target, and to determine its pharmacological effect,” said Dr Ventura.

“In this study we were able to conclude that stinging nettle leaf extract reduces contractility of urinary and genital smooth muscle by acting as a P2X1-purinoceptor antagonist, and that blocking sperm transport through pharmacological blockade of P2X1-purinoceptors via oral administration is an effective and convenient biological strategy for male contraception.”

The next step for this research is to isolate the bioactive component of this extract or identify a similar compound suitable for chemical optimization to use as a male contraceptive.

At the moment the options for male contraception include only condoms and vasectomy, with the burden of preventing pregnancy largely and unevenly falling on women or people with a uterus.

“Unfortunately there has been a widespread perception that birth control is a women’s problem rather than a men’s problem,” said Dr Ventura.

“However research led by the Male Contraceptive Initiative shows that the majority of men are willing to take control over contraception – we just need to give them the opportunity to do so.”

To read the full article entitled Aqueous extracts of Urtica dioica (stinging nettle) leaf contain a P2-purinoceptor antagonist—Implications for male fertility visit: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271735

 

 

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