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Parkinson’s, Cancer, and Type 2 Diabetes Share a Key Element That Drives Disease

Parkin protein (green signal) is in a different part of the cell than the mitochondria (red signal) at time 0 (left image) but then co-localizes with the mitochondria after 60 minutes (right image). Credit: Salk Institute

Enzyme with central role in cancer and type 2 diabetes also activates “clean-up” protein in Parkinson’s.

When cells are stressed, chemical alarms go off, setting in motion a flurry of activity that protects the cell’s most important players. During the rush, a protein called Parkin hurries to protect the mitochondria, the power stations that generate energy for the cell. Now Salk researchers have discovered a direct link between a master sensor of cell stress and Parkin itself. The same pathway is also tied to type 2 diabetes and cancer, which could open a new avenue for treating all three diseases.

“Our findings represent the earliest step in Parkin’s alarm response that anyone’s ever found by a long shot. All the other known biochemical events happen at one hour; we’ve now found something that happens within five minutes,” says Professor Reuben Shaw, director of the NCI-designated Salk Cancer Center and senior author of the new work, detailed in Science Advances on April 7, 2021. “Decoding this major step in the way cells dispose of defective mitochondria has implications for a number of diseases.”

Parkin’s job is to clear away mitochondria that have been damaged by cellular stress so that new ones can take their place, a process called mitophagy. However, Parkin is mutated in familial Parkinson’s disease, making the protein unable to clear away damaged mitochondria. While scientists have known for some time that Parkin somehow senses mitochondrial stress and initiates the process of mitophagy, no one understood exactly how Parkin was first sensing problems with the mitochondria—Parkin somehow knew to migrate to the mitochondria after mitochondrial damage, but there was no known signal to Parkin until after it arrived there.

Shaw’s lab, which is well known for their work in the fields of metabolism and cancer, spent years intensely researching how the cell regulates a more general process of cellular cleaning and recycling called autophagy. About ten years ago, they discovered that an enzyme called AMPK, which is highly sensitive to cellular stress of many kinds, including mitochondrial damage, controls autophagy by activating an enzyme called ULK1.

Following that discovery, Shaw and graduate student Portia Lombardo began searching for autophagy-related proteins directly activated by ULK1. They screened about 50 different proteins, expecting about 10 percent to fit. They were shocked when Parkin topped the list. Biochemical pathways are usually very convoluted, involving up to 50 participants, each activating the next. Finding that a process as important as mitophagy is initiated by only three participants—first AMPK, then ULK1, then Parkin—was so surprising that Shaw could scarcely believe it.

To confirm the findings were correct, the team used mass spectrometry to reveal precisely where ULK1 was attaching a phosphate group to Parkin. They found that it landed in a new region other researchers had recently found to be critical for Parkin activation but hadn’t known why. A postdoctoral fellow in Shaw’s lab, Chien-Min Hung, then did precise biochemical studies to prove each aspect of the timeline and delineated which proteins were doing what, and where. Shaw’s research now begins to explain this key first step in Parkin activation, which Shaw hypothesizes may serve as a “heads-up” signal from AMPK down the chain of command through ULK1 to Parkin to go check out the mitochondria after a first wave of incoming damage, and, if necessary, trigger destruction of those mitochondria that are too gravely damaged to regain function.

The findings have wide-ranging implications. AMPK, the central sensor of the cell’s metabolism, is itself activated by a tumor suppressor protein called LKB1 that is involved in a number of cancers, as established by Shaw in prior work, and it is activated by a type 2 diabetes drug called metformin. Meanwhile, numerous studies show that diabetes patients taking metformin exhibit lower risks of both cancer and aging comorbidities. Indeed, metformin is currently being pursued as one of the first ever “anti-aging” therapeutics in clinical trials.

“The big takeaway for me is that metabolism and changes in the health of your mitochondria are critical in cancer, they’re critical in diabetes, and they’re critical in neurodegenerative diseases,” says Shaw, who holds the William R. Brody Chair. “Our finding says that a diabetes drug that activates AMPK, which we previously showed can suppress cancer, may also help restore function in patients with neurodegenerative disease. That’s because the general mechanisms that underpin the health of the cells in our bodies are way more integrated than anyone could have ever imagined.”

Reference: “AMPK/ULK1-mediated phosphorylation of Parkin ACT domain mediates an early step in mitophagy” by Chien-Min Hung, Portia S. Lombardo, Nazma Malik, Sonja N. Brun, Kristina Hellberg, Jeanine L. Van Nostrand, Daniel Garcia, Joshua Baumgart, Ken Diffenderfer, John M. Asara and Reuben J. Shaw, 7 April 2021, Science Advances.
DOI: 10.1126/sciadv.abg4544

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This post originally posted here The European Times News

Diabetes type 2 symptoms: Three skin conditions indicative of high blood sugar

The global diabetes community draw attention to necrobiosis lipoidica diabeticorum (NLD) – a skin condition whereby lesions develop on the lower parts of the legs. Described as “shiny” and “red-brown” in colour, the patches can be between 1-2mm in size. As time goes on, these small patches can grow bigger and bigger, becoming progressively yellow in colouring. Interestingly, the presence of NLD preceded the onset of diabetes in 15 percent of patients involved in a research study conducted by MH Lowitt and JS Dover.

The American Diabetes Association added that some people with high blood sugar might experience diabetic dermopathy.

This skin condition looks like “light brown, scaly patches” that are oval or circular in shape.

Easily mistaken as age spots, patches of diabetic dermopathy typically occur on the shins.

Medical News Today pointed out that the marks may come and go, but tend to appear on both shins at the same time, usually measuring up to 2.5cm or less.

How to lower high blood sugar levels

The NHS recommend exercising more often to help lower blood sugar levels.

This might involve going for a brisk 30-minute walk daily, which can be extremely helpful in preventing further health complications.

The national health body also advise to “drink plenty of sugar-free fluids”, such as water.

You also need to be mindful of what you eat, avoiding foods that can cause blood sugar levels to spike, such as cakes.

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This post originally posted here Daily Express :: Health
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Type 2 diabetes: The palm test that could identify high blood sugar complications

According to the global diabetes community, stiffness begins in the little finger and spreads to the thumb when you have diabetic cheiroarthropathy. Limited finger movement is paired with waxy, thickened skin on the hands. Over time, if you bring your palms together, the fingers may not be able to touch if you have this condition. If there is a gap between your fingers and palms in this position, you’re advised to see your doctor.

Symptoms of this diabetes complication are often worse at night and include:

  • Numbness or reduced ability to feel pain or temperature changes
  • Tingling or burning sensation
  • Sharp pains or cramps
  • Increased sensitivity to touch — for some people, even a bedsheet’s weight can be painful
  • Serious foot problems, such as ulcers, infections, and bone and joint pain.

If the autonomic nervous system starts to fail due to nerve damage, it can cause bladder or bowel issues.

You may feel nauseous, lose your appetite, and vomit as the digestive system is affected.

Proximal neuropathy can then lead to severe stomach pain, hip, thigh or buttock pain.

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It can also cause difficulty for people trying to rise up from a sitting position.

Mononeuropathy can lead to an achy feeling behind one eye, difficulty focusing, double vision, or numbness or tingling in the hands or fingers, except for the pinkie.

The NHS warned that uncontrolled and persistent high blood sugar levels can lead to numerous health issues.

For instance, the condition could lead to heart disease and stroke, blindness, and sexual impotency.

People with diabetes are encouraged to go for regular health check-ups.

A diabetes nurse of doctor should be checking your blood sugar levels every six months.

Then, once a year, you need to be checked over for any loss of feeling in your feet, signs of ulcers or infections.

“Speak to your GP immediately if you have cuts, bruises or numbness in your feet,” instructed the NHS.

Your doctor should also check your blood pressure and cholesterol levels.

It’s also important to get your vision checked every year too; this is so any health complications can be picked up on in the early stages.

Keeping on top of your health is one way to help prevent complications from developing or worsening.

For more support and information on managing type 2 diabetes, please visit the charity Diabetes UK.

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This post originally posted here Daily Express :: Health
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Type 2 diabetes: Four ‘serious’ foot problems that signal blood sugar damage to nerves

In addition to symptoms, you should also see a GP if you’re worried you may have a higher risk of getting type 2 diabetes, advises the NHS.

Following a formal diagnosis, your GP will usually recommend changing aspects of your lifestyle to bring blood sugar levels under control, notes the health body.

There are two key components of blood sugar control – diet and exercise.

“Diabetes won’t stop you from enjoying your food, but knowing some simple hacks and swaps will help you choose healthier options and make planning your meals a little easier,” explains Diabetes UK.

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This post originally posted here Daily Express :: Health
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Diabetes type 2: The sign of blood sugar in your feet that could lead to amputation

That’s because carbs are broken down into glucose (blood sugar) relatively fast, which can cause a marked rise in blood sugar levels.

“Vegetables, fruits, and whole grains provide more nutrition per calorie than refined carbohydrates and tend to be rich in fibre,” notes Harvard Health.

As it explains, “your body digests high-fibre foods more slowly — which means a more moderate rise in blood sugar”.

The health body adds: “Avoid highly refined carbohydrates such as white bread, pasta, and rice, as well as candy, sugary soft drinks, and sweets.”

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Diabetes type 2 prevention: How the dangerous condition can be prevented

Even if you’re at increased risk of type 2 diabetes – due to a hereditary link or having gestational diabetes – there are things you can do to help minimise the chances of developing the condition. The “most important” lifestyle change you can make, according to the Global Diabetes Community, is altering your diet. “Cutting out sugary food and drink, and refined grains – such as white bread and white rice – is a good first step,” the community said.

Any BMI of 25 or over is considered “overweight”; you can lower your BMI through a combination of diet and exercise.

The NIH recommends people who want to prevent type 2 diabetes to do “at least 30 minutes of physical activity, five days per week”.

This can help you to lose weight and to keep it off, which can delay the development of type 2 diabetes.

The Global Diabetes Community stated: “Exercise can help to prevent diabetes in a number of ways.”

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The American Diabetes Association explained: “When your muscles contract during activity, your cells are able to take up glucose and use it for energy whether insulin is available or not.”

This means that the level of glucose in the blood (i.e. blood sugar) decreases.

Exercise also increases insulin sensitivity, meaning the body’s cells are better able to use available insulin to absorb glucose.

To explain, insulin is a hormone released by the pancreas when blood sugar levels increase.

Insulin is the key that enables glucose to be absorbed from the blood into the body’s cells to be used as fuel.

“The effect physical activity has on your blood sugar will vary depending on how long you are active and many other factors,” said the American Diabetes Association.

“Physical activity can lower your blood sugar up to 24 hours or more after your workout by making your body more sensitive to insulin.”

The charity Diabetes UK stated “lifestyle interventions – including diet, physical activity and sustained weight loss – can be effective in reducing the risk of type 2 diabetes by about 50 percent”.

Dietary swaps to prevent type 2 diabetes

Choose wholegrain carbohydrates such as brown rice, wholewheat pasta, wholemeal flour, and wholegrain bread.

Other healthy sources of carbohydrates include fruit and vegetables, chickpeas, beans, lentils, and unsweetened yoghurt and milk.

It’s important to “cut down on red and processed meat”, such as:

  • Bacon
  • Ham
  • Sausages
  • Pork
  • Beef
  • Lamb.

Instead, opt for oily fish such as salmon and mackerel, which are rich in omega-3.

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Diabetes type 2: A ‘superior’ weight loss drug lowers high blood sugar

The National Institute for Health and Care Excellence (NICE) confirmed that semaglutide increases insulin secretion by binding to, and activating, the GLP-1 (glucagon-like peptide-1) receptor. Semaglutide also suppresses glucagon secretion and slows gastric emptying, meaning those who take it feel fuller for longer. Other side effects of the medication may include: constipation, diarrhoea, dizziness, fatigue, and gastrointestinal discomfort.

New research – published in The New England Journal of Medicine – shows that tirzepatide achieved superior results compared to semagutide.

In the 40-week trial, tirzepatide lowered blood sugar levels more than 1mg injectables of semagutide in people with type 2 diabetes.

Participants who had the highest dose of tirzepatide lost 12.4kg compared to 6.2kg for those on semaglutide.

Knowing that obesity is a risk factor for developing type 2 diabetes, and that remission can be achieved via weight loss, the researchers are very excited about the results.

READ MORE: Diabetes diet: Four ‘diabetes friendly’ spices to avoid high blood sugar symptoms

Dr Kunal Gulati – a leader in diabetes care at Lilly, Northern Europe (who research and develop innovative medicines) – is chuffed with the “meaningful” results.

“As a leader in diabetes care, Lilly is proud to be researching and developing solutions that can lead to meaningful HbA1C [blood sugar] reductions,” he said.

A 15mg dose of tirzepatide lowered blood sugar levels, on average, by -2.46 percent.

Even a 5mg dose of tirzepatide lowered blood sugar levels by around -2.09 percent.

If you’re concerned you might have diabetes, the symptoms to look out for include:

  • Peeing more than usual, particularly at night
  • Feeling thirsty all the time
  • Feeling very tired
  • Losing weight without trying to
  • Itching around your penis or vagina, or repeatedly getting thrush
  • Cuts or wounds taking longer to heal
  • Blurred vision.

Having high blood sugars can damage blood vessels, leading to further health complications.

This is why it’s so important to lower blood sugar levels, and to take any medication that is prescribed to you, including semaglutide.

Author: Chanel Georgina
Read more here >>> Daily Express :: Health
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Diabetes type 2 symptoms: Eight of the most ‘common’ signs of high blood sugar

An earlier diabetes diagnosis could reduce the chances of developing other long-term health problems, as you’ll be advised on how best to manage your blood sugar levels by a doctor or nurse. The progression of symptoms is gradual in type 2 diabetes, so these signs can occur across a number of years. Do take note if you find yourself going to the toilet more than before, especially if it’s during the night.

Another “common” symptom of high blood sugar – the indicator of type 2 diabetes – is feeling “really thirsty”, the charity Diabetes UK noted.

It’s also fairly typical to experience feelings of tiredness, increased hunger, and blurred eyesight.

Diabetes can also lead to recurrent bouts of genital itching or thrush, and cuts and wounds may take longer to heal.

Some people might lose weight without meaning to, which is also another possible sign of type 2 diabetes.

READ MORE: Diabetes diet: Four ‘diabetes friendly’ spices to avoid high blood sugar symptoms

Instead, when your pancreas isn’t creating quality insulin, glucose builds up in the bloodstream.

The body breaks down the carbohydrates you get from food and drink into glucose.

Thus, if the glucose isn’t moving from the bloodstream into the body’s cells, over time, more and more glucose takes up space in the bloodstream.

High blood sugar can damage every part of the body, including the eyes, heart, and feet.

While there is no cure for type 2 diabetes, people have been able to put their condition into remission.

This means blood sugar levels are at the pre-diabetes level without taking medication.

This can be achieved by weight loss, according to the latest research on type 2 diabetes.

“If you have obesity, you are more likely to put your diabetes into remission if you lose a substantial amount of weight,” said Diabetes UK.

People who fall into the obese category (having a body mass index of 30 or more) need to lose 2st 5lbs.

Carrying excess weight around the tummy area can increase the likelihood of visceral fat building up around the organs, such as the pancreas.

When there is too much visceral fat around the pancreas, for example, the gland may not work properly anymore, leading to type 2 diabetes.

“But not everyone who develops type 2 diabetes has obesity,” warned the charity.

Author: Chanel Georgina
Read more here >>> Daily Express :: Health
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Diabetes type 2: Experts discuss the optimal breakfast for blood sugar and what to avoid

“Don’t be hoodwinked into thinking breakfast cereals that appear healthy – are indeed healthy,” added Dr Lee.

“Many different brands that look and sound like they must be good for you, such as muesli or granola, are often packed with sugar.

“For example, some types of granola contain 17 g of sugar per serving – around four teaspoons.

“Each teaspoon of sugar equates to around 5 g of carbohydrate.

“The problem gets worse because often people often eat more than one serving. And that’s before you’ve added the milk.

“Always check the label and make sure you are eating no-sugar cereal. Check the packaging and look for the green label.

“Cereals that are excellent for diabetics include porridge, wheat biscuits, and shredded wheat.”

Author: Jessica Knibbs
This post originally appeared on Daily Express :: Health
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ADA Guidance: Bring Type 1 Diabetes in Adults Out of the Shadows

A new draft consensus statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) addresses diagnosis and management of type 1 diabetes in adults.

Type 1 Diabetes in Adults Out of the Shadows

The impetus for the document comes from the “highly influential” EASD-ADA consensus report on the management of type 2 diabetes, which led to the realization that a comparable document was needed for adults with type 1 diabetes, said writing panel cochair Anne L. Peters, MD, professor of clinical medicine at Keck School of Medicine, University of Southern California, Los Angeles

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Read more on Medscape Medical News Headlines