Tag: insulin

Categories : Genetics Metabolic DisordersTags :

Smart Moo-ve for Diabetes Treatment: Insulin Produced in Cow’s Milk

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Photo by Pixabay on Pexels

An unassuming brown bovine from the south of Brazil has made history as the first transgenic cow capable of producing human insulin in her milk. The advancement, led by researchers from the University of Illinois Urbana-Champaign and the Universidade de São Paulo, could herald a new era in insulin production, one day eliminating drug scarcity and high costs for people living with diabetes.

“Mother Nature designed the mammary gland as a factory to make protein really, really efficiently. We can take advantage of that system to produce a protein that can help hundreds of millions of people worldwide,” said Matt Wheeler, professor in the Department of Animal Sciences, part of the College of Agricultural, Consumer and Environmental Sciences (ACES) at U. of I.

Wheeler is lead author on a new Biotechnology Journal study describing the development of the insulin-producing cow, a proof-of-concept achievement that could be scaled up after additional testing and FDA approval.

Precise insertion of DNA

Wheeler’s colleagues in Brazil inserted a segment of human DNA coding for proinsulin – the protein precursor of the active form of insulin – into cell nuclei of 10 cow embryos. These were implanted in the uteruses of normal cows in Brazil, and one transgenic calf was born. Thanks to updated genetic engineering technology, the human DNA was targeted for expression – the process whereby gene sequences are read and translated into protein products – in mammary tissue only.

“In the old days, we used to just slam DNA in and hope it got expressed where you wanted it to,” Wheeler said. “We can be much more strategic and targeted these days. Using a DNA construct specific to mammary tissue means there’s no human insulin circulating in the cow’s blood or other tissues. It also takes advantage of the mammary gland’s capabilities for producing large quantities of protein.”

When the cow reached maturity, the team unsuccessfully attempted to impregnate her using standard artificial insemination techniques. Instead, they stimulated her first lactation using hormones. The lactation yielded milk, but a smaller quantity than would occur after a successful pregnancy. Still, human proinsulin and, surprisingly, insulin were detectable in the milk.

“Our goal was to make proinsulin, purify it out to insulin, and go from there. But the cow basically processed it herself. She makes about three to one biologically active insulin to proinsulin,” Wheeler said. “The mammary gland is a magical thing.”

The insulin and proinsulin, which would need to be extracted and purified for use, were expressed at a few grams per liter in the milk. But because the lactation was induced hormonally and the milk volume was smaller than expected, the team can’t say exactly how much insulin would be made in a typical lactation.

Conservatively, Wheeler says if a cow could make 1 gram of insulin per liter and a typical Holstein makes 40 to 50 litres per day, that’s a lot of insulin. Especially since the typical unit of insulin equals 0.0347 milligrams.

“That means each gram is equivalent to 28,818 units of insulin,” Wheeler said. “And that’s just one liter; Holsteins can produce 50 liters per day. You can do the math.”

The team plans to re-clone the cow, and is optimistic they’ll achieve greater success with pregnancy and full lactation cycles in the next generation. Eventually, they hope to create transgenic bulls to mate with the females, creating transgenic offspring that can be used to establish a purpose-built herd. Wheeler says even a small herd could quickly outcompete existing methods – transgenic yeast and bacteria – for producing insulin, and could do so without having to create highly technical facilities or infrastructure.

“With regard to mass-producing insulin in milk, you’d need specialized, high-health-status facilities for the cattle, but it’s nothing too out of the ordinary for our well-established dairy industry,” Wheeler said. “We know what we’re doing with cows.”

An efficient system to collect and purify insulin products would be needed, as well as FDA approval, before transgenic cows could supply insulin for the world’s diabetics. But Wheeler is confident that day is coming.

“I could see a future where a 100-head herd, equivalent to a small Illinois or Wisconsin dairy, could produce all the insulin needed for the country,” he said. “And a larger herd? You could make the whole world’s supply in a year.

Source: University of Illinois College of Agricultural, Consumer and Environmental Sciences

Categories : Metabolic DisordersTags :

New Nanoparticle-based Oral Insulin could be Ready for Human Trials Next Year

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Photo by Nataliya Vaitkevich on Pexels

Scientists have developed a ‘smart’ insulin which can be taken orally. The insulin is encapsulated within tiny nano-carriers, 1/10 000th the width of a human hair. The results of its testing in baboons were recently published in Nature Nanotechnology.

“This way of taking insulin is more precise because it delivers the insulin rapidly to the areas of the body that need it most. When you take insulin with a syringe, it is spread throughout the body where it can cause unwanted side effects,” explains Professor Peter McCourt at UiT Norway’s Arctic University. He is one of the researchers behind the study.

Delivered insulin to where it’s needed

It was researchers at the University of Sydney and Sydney Local Health District who, in collaboration with UiT, discovered many years ago that it was possible to deliver medicines via nano-carriers to liver. The method has then been further developed in Australia and in Europe.

Many medicines can be taken orally, but until now people have had to inject insulin into the body. McCourt explains that the problem with insulin with a nano-carrier is that it breaks down in the stomach and thus does not get to where it is needed in the body. This has been a major challenge for developing a diabetes medicine that can be taken orally.

But now the researchers have solved this challenge.

“We have created a coating to protect the insulin from being broken down by stomach acid and digestive enzymes on its way through the digestive system, keeping it safe until it reaches its destination, namely the liver,” says McCourt, who is a liver biologist.

The coating is then broken down in the liver by enzymes that are active only when the blood sugar levels are high, releasing the insulin where it can then act in the liver, muscle, and fat to remove sugar from the blood.

“This means that when blood sugar is high, there is a rapid release of insulin, and even more importantly, when blood sugar is low, no insulin is released,” says Nicholas J. Hunt at the University of Sydney who, together with Victoria Cogger, leads the project.

He explains that this is a more practical and patient-friendly method of managing diabetes because it greatly reduces the risk of a low blood sugar event occurring, namely hypoglycaemia and allows for the controlled released of insulin depending on the patient’s needs, unlike injections where all the insulin is released in one shot.

Fewer side effects

The new method works similarly to how insulin works in healthy people. The pancreas produces insulin which first passes through the liver where a large portion of it is absorbed and maintains stable blood sugar levels. In the new insulin method, the nano-carrier releases insulin in the liver, where it can be taken up or enter the blood to circulate in the body.

When insulin is injected subcutaneously, far more of it goes to the muscles and to adipose tissues that would normally happen if it was released from the pancreas, which can lead to fat accumulation. It can also lead to hypoglycaemia.

With the new method, there will be fewer such side effects, and no need for injection – or refrigeration.

Tested on baboons

The oral insulin has been tested on nematodes, on mice and rats. And lastly, the medicine has now been tested on baboons in the National Baboon Colony in Australia.

“In order to make the oral insulin palatable we incorporated it into sugar-free chocolate, this approach was well received” says Hunt.

He says that 20 baboons have taken part in this study. When they received the medicine, their blood sugar was lowered.

The baboons were normal, healthy baboons, but the oral insulin have also been tested on mice and rats that actually have diabetes. The mice and rats did not have hypoglycaemic events, gain weight or fat accumulation in the liver overcoming current challenges with injectable and other oral insulins.

What remains now is to test the new method on humans.

Ready for use in 2-3 years

“Trials on humans will start in 2025 led by the spin out company Endo Axiom Pty Ltd. Clinical trials are performed in 3 phases; in the phase I trial we will investigate the safety of the oral insulin and critically look at the incidence of hypoglycaemia in healthy and type 1 diabetic patients. Our team is very excited to see if we can reproduce the absent hypoglycaemia results seen in baboons in humans as this would be a huge step forward. The experiments follow strict quality requirements and must be carried out in collaboration with physicians to ensure that they are safe for the test subjects” says Hunt.

Source: UiT The Arctic University of Norway

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

Macrophages ‘Eat’ Pancreatic β Cells to Regulate Insulin Post Partum

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A 3D map of the islet density routes throughout the healthy human pancreas. Source: Wikimedia CC0

Scientists have long known that pancreatic β cells increase during pregnancy and promptly return to their original number following birth. But the underlying mechanisms that cause the cells to go back to their original number are still not well understood.

In a significant breakthrough, a research group using mouse models, has discovered that macrophages ‘eat’ (phagocytose) the pancreatic β cells, thereby revealing the process behind their return to previous levels after pregnancy.

The research group, which was led by Associate Professor Junta Imai, Assistant Professor Akira Endo, and Professor Hideki Katagiri from Tohoku University’s Graduate School of Medicine, published the results in the journal Development Cell.

Initially, the group examined the number of pancreatic β cells in the islets of Langerhans in a mouse model of pregnancy.

They confirmed the cell number was double at the end of the pregnancy when compared to non-pregnant mice, but that it then gradually decreased, returning to the original amount after delivery.

“After we observed the islets of Langerhans before and after delivery, we noticed an increase in macrophages, which protect the body from infections by engulfing bacteria, foreign substances and dead cells, after delivery,” says Imai.

“When we applied treatment to inhibit this process, the blood glucose levels became too low (hypoglycaemia).”

Additional microscopic observation of the islets of Langerhans after birth revealed β cells to be phagocytosed by macrophages.

This mechanism appeared to keep the mother’s blood glucose levels from decreasing excessively after delivery by rapidly reducing pancreatic β cells to their normal pre-pregnancy number.

Next, the group identified the protein responsible for attracting the macrophages into the islets of Langerhans: cytokine CXCL10.

Accordingly, the inhibition of CXCL10 function suppressed the decrease in pancreatic β cells after birth.

“We hope our results will contribute to clarifying the means by which normal blood glucose levels are maintained as well as the development of methods to prevent and treat diabetes,” adds Imai.

Source: Tohoku University

Categories : Metabolic DisordersTags :

Review Shows that Insulin can be Kept at Room Temperature for Longer

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Novolog insulin pen. Photo by Dennis Klicker on Unsplash

A new Cochrane review has found that insulin can be kept at room temperature for months without losing potency, offering hope to people living with diabetes in regions with limited access to healthcare or stable powered refrigeration. This affects millions of people living in low- and middle-income countries, particularly in rural areas, as well as people whose lives have been disrupted by conflict or natural disasters.

Insulin is an essential medicine for people with diabetes and current guidance states that before use it must be kept refrigerated to preserve its effectiveness. For millions of people with diabetes living in low- and middle-income countries, however, the harsh reality is that electricity and refrigeration are luxuries that are unavailable to them. Vulnerable populations in war-torn areas, disaster-prone regions, and climate crisis-affected areas, including those enduring extreme heat, also need solutions that don’t rely on powered fridges.

The new Cochrane review summarises results of different studies investigating what happens to insulin when stored outside of fridges, including previously unpublished data from manufacturers. The review found that it is possible to store unopened vials and cartridges of specific types of human insulin at temperatures of up to 25°C for a maximum of six months, and up to 37°C for a maximum of two months, without any clinically relevant loss of insulin activity. Data from one study showed no loss of insulin activity for specific insulin types when stored in oscillating ambient temperatures of between 25°C and 37°C for up to three months. This fluctuation resembles the day-night temperature cycles experienced in tropical countries.

The research team, led by Bernd Richter from the Institute of General Practice, Medical Faculty of the Heinrich-Heine-University in Düsseldorf, Germany, conducted comprehensive research to investigate insulin stability under various storage conditions. The review analysed a total of seventeen studies, including laboratory investigations of insulin vials, cartridges/pens, and prefilled syringes, demonstrating consistent insulin potency at temperatures ranging from 4°C to 37°C, with no clinically relevant loss of insulin activity.

Bernd stressed the significance of this research, particularly for people living with type 1 diabetes, where “insulin is a lifeline, as their very lives depend on it. While type 2 diabetes presents its challenges, type 1 diabetes necessitates insulin for survival. This underscores the critical need for clear guidance for people with diabetes in critical life situations, which many individuals lack from official sources.

“Our study opens up new possibilities for individuals living in challenging environments, where access to refrigeration is limited. By understanding the thermal stability of insulin and exploring innovative storage solutions, we can make a significant impact on the lives of those who depend on insulin for their well-being.”

These findings can help communities facing challenges in securing constant cold storage of insulin. They provide reassurance that alternatives to powered refrigeration of insulin are possible without compromising the stability of this essential medicine. It suggests that if reliable refrigeration is not possible, room temperature can be lowered using simple cooling devices such as clay pots for insulin storage.

The researchers have also identified uncertainties for future research to address. There remains a need to better understand insulin effectiveness following storage under varying conditions. Further research is also needed on mixed insulin, influence of motion for example when insulin pumps are used, contamination in opened vials and cartridges, and studies on cold environmental conditions.

Source: Cochrane Reviews

Categories : Metabolic DisordersTags :

Daily Insulin Injections Could be Replaced with Weekly Ones

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Novolog insulin pen. Photo by Dennis Klicker on Unsplash

Insulin icodec, a once-weekly basal injection to treat type 1 diabetes, has the potential to be as effective in managing the condition as daily basal insulin treatments, according to research from the University of Surrey. The results of the year-long phase 3 clinical trial were published in The Lancet, and could one day revolutionise diabetes care.

During this pioneering study, scientists across 12 countries at 99 sites, led by Professor David Russell-Jones from Surrey, tested the efficacy and safety of a weekly basal injection of icodec (a long-lasting type of insulin) and compared it to a daily basal injection of insulin degludec in adults with type 1 diabetes. Short acting insulin to cover meals was used in both groups.

Professor David Russell-Jones, Professor of Diabetes and Endocrinology at the University of Surrey and a Consultant at the Royal Surrey Foundation Trust, said:

“Many people find managing a long-term condition such as diabetes very difficult and report missing vital insulin injections. Missed injections can affect glycaemic control, and a lack of consistency in the treatment has been linked to increased rates of diabetic ketoacidosis, a serious complication of the condition that can be life-threatening. Reducing insulin injection frequency could lessen the burden of treatment for some people with the condition and improve their glycaemic control.”

To learn more about the efficacy of icodec, scientists recruited 582 participants with type 1 diabetes. Participants were split into two groups; the first received once-weekly injections of icodec (700U/mL), and the second received daily injections of degludec (100U/mL), both in combination with aspart, a short-acting insulin at mealtimes.

After 26 weeks, scientists identified HbA1C levels in those who had taken icodec had decreased from a mean of 7.59% at baseline to an estimated mean of 7.15% , and for degludec, the mean had fallen from 7.63% to 7.10%. The estimated treatment difference between them being 0.05 percent, confirming the non-inferiority of icodec to degludec, but with a significantly reduced injection frequency for patients to manage.

Scientists did also identify higher rates of hypoglycaemic episodes (abnormally low levels of glucose in the blood) in the icodec group compared to degludec. However, despite the higher levels in the icodec group, scientists noted that incidences were low in both groups, with most episodes only requiring oral carbohydrate administration. For icodec, time below 3.0mmol/L was at the threshold of the internationally recommended targets during weeks 22-26 and below recommended targets during weeks 48-52.

Professor Russell-Jones added:

“What we have found is that once-weekly icodec injections showed non inferiority to once-daily injections of degludec in reducing HbA1C after 26 weeks. Although there is a slightly higher rate of hypoglycaemia under this regime, we found this could be easily managed. We’ve concluded this new insulin may have a role in reducing the burden of daily basal injections for patients managing type 1 diabetes.

“Our findings are very promising, but further analysis of continuous glucose monitoring data and real-world studies are needed.”

Source: University of Surrey

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

Metformin Trial Offers Hope for Women with Gestational Diabetes

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Source: Pixabay CC0

A significant step forward has been taken in the management of gestational diabetes mellitus after a clinical trial involving pregnant women provided new hope for expectant mothers suffering the condition. The findings from the trial are published in the Journal of American Medical Association.

Gestational diabetes affects almost 3 million pregnant women worldwide every year. It is a condition characterised by elevated blood sugar levels during pregnancy, posing increased health risks for both mothers and their babies.

The EMERGE, randomised, placebo-controlled trial, was conducted by the University of Galway and involved more than 500 pregnant women.

The trial results showed that:

  • Women assigned to metformin were 25% less likely to need insulin, and when insulin was necessary, it was started later in the pregnancy.
  • Fasting and post-meal glycaemic values in the mother were significantly lower in the metformin exposed group at weeks 32 and 38.
  • Women receiving metformin gained less weight throughout the trial and maintained this weight difference at the 12-week post-delivery visit.
  • Importantly, delivery occurred at the same mean gestational age (39.1 weeks) in both groups. There was no evidence of any increase in preterm birth (defined as birth before 37 weeks) among those who received metformin.
  • Infants born to mothers who received metformin weighed, on average, 113g less at birth, with significantly fewer infants classified as large at birth, or weighing over 4kg.
  • While there was a slight reduction in infant length (0.7cm), there were no other significant differences in baby measurements.
  • There were slightly more babies who were small at birth but this did not reach statistical significance.

The study also revealed no differences in adverse neonatal outcomes, including the need for intensive care treatment for new-borns, respiratory support, jaundice, congenital anomalies, birth injuries or low sugar levels.

Additionally there were no variations in rates of labour induction, caesarean delivery, maternal haemorrhage, infection or blood pressure issues during or after birth.

Professor Fidelma Dunne managed the trial, and presented the results at the 59th Annual Meeting of the European Association for the Study of Diabetes in Hamburg, Germany.

Professor Dunne said, “While there is convincing evidence that improved sugar control is associated with improved pregnancy outcomes, there was uncertainty about the optimal management approach following a diagnosis of gestational diabetes.

“In our pursuit of a safe and effective treatment option we explored an alternative approach – administering the drug metformin. A previous trial compared metformin to insulin and found it to be effective, yet concerns remained, especially regarding preterm birth and infant size.”

To address concerns comprehensively, the team at University of Galway conducted a ground-breaking placebo-controlled-trial, filling a critical gap in the gestational diabetes treatment landscape.

  • 535 pregnant women took part, with 268 receiving metformin and 267 a placebo.
  • 98% of women remained in the trial until delivery, with 88% completing the 12-week post-delivery follow up assessment.
  • Only 4.9% of women discontinued medication due to side effects, highlighting the safety of the interventions.

Professor Dunne said, “Traditionally, gestational diabetes has been managed initially through dietary advice and exercise, with insulin introduced if sugar levels remain sub optimal. While effective in reducing poor pregnancy outcomes, insulin use is associated with challenges, including low sugars in both the mother and infant which may require neonatal intensive care, excess weight gain for mothers, and higher caesarean birth rates.” Professor Dunne added: “The results from the EMERGE study are a significant step forward for women with gestational diabetes. Metformin has emerged as an effective alternative for managing gestational diabetes, offering new hope for expectant mothers and healthcare providers worldwide.”

Source: University of Galway

Categories : Medical Research & Technology Metabolic DisordersTags :

‘We Will Rock You’: The Special Cells that Secrete Insulin to Music

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Freddie Mercury performing with Queen in 1977. Source: Wikimedia Commons

Music has often been touted as a soothing treatment to aid healing. Now, researchers at ETH Zurich in Basel have come up with another medical approach. They have developed a novel method to get music to make specially designed cells secrete insulin. They found that this works especially well with the bass rhythm “We Will Rock You,” a global hit by British rock band, Queen.

Diabetics depend on an external supply of insulin via injection or pump. Researchers led by Martin Fussenegger from the Department of Biosystems Science and Engineering at ETH Zurich in Basel want to make the lives of these people easier and are looking for solutions to produce and administer insulin directly in the body. Any alternatives must be able to release insulin in controlled quantities on command.

One such solution the scientists are pursuing is enclosing insulin-producing designer cells in capsules that can be implanted in the body. To be able to control from the outside when and how much insulin the cells release into the blood, researchers have studied and applied different triggers in recent years: light, temperature and electric fields.

Equipping cells to receive sound waves

To make the insulin-producing cells receptive to sound waves, the researchers used a protein from the bacterium E. coli. Such proteins respond to mechanical stimuli and are common in animals and bacteria. The protein is located in the membrane of the bacterium and regulates the influx of calcium ions into the cell interior. The researchers incorporated the blueprint of this bacterial ion channel into human insulin-producing cells, letting these cells create the ion channel themselves and embed it in their membrane.

As the scientists have been able to show, the channel in these cells opens in response to sound, allowing positively charged calcium ions to flow into the cell. This leads to a charge reversal in the cell membrane, which in turn causes the tiny insulin-filled vesicles inside the cell to fuse with the cell membrane and release the insulin to the outside.

Turn up the bass

In cell cultures, the researchers first determined which frequencies and volume levels activated the ion channels most strongly. They found that volume levels around 60 decibels (dB) and bass frequencies of 50 hertz were the most effective in triggering the ion channels. To trigger maximum insulin release, the sound or the music had to continue for a minimum of three seconds and pause for a maximum of five seconds. If the intervals were too far apart, substantially less insulin was released.

Finally, the researchers looked into which music genres caused the strongest insulin response at a volume of 85dB. Rock music with booming bass like the song “We Will Rock You,” from Queen, came out on top, followed by the soundtrack to the action movie The Avengers. The insulin response to classical music and guitar music was rather weak by comparison.

“We Will Rock You” triggered roughly 70% of the insulin response within five minutes, and all of it within 15 minutes. This is comparable to the natural glucose-induced insulin response of healthy individuals, Fussenegger says.

Sound source must be directly above the implant

To test the system as a whole, the researchers implanted the insulin-producing cells into mice and placed the animals so that their bellies were directly on the loudspeaker. This was the only way the researchers could observe an insulin response. If, however, the animals were able to move freely in a “mouse disco,” the music failed to trigger insulin release.

“Our designer cells release insulin only when the sound source with the right sound is played directly on the skin above the implant,” Fussenegger explains. The release of the hormone was not triggered by ambient noise such as aircraft noise, lawnmowers, fire brigade sirens or conversations.

Ambient noise won’t do

As far as he can tell from tests on cell cultures and mice, Fussenegger sees little risk that the implanted cells in humans would release insulin constantly and at the slightest noise.

Another safety buffer is that insulin depots need four hours to fully replenish after they have been depleted. So even if the cells were exposed to sound at hourly intervals, they would not be able to release a full load of insulin each time and thereby cause life-threatening hypoglycaemia. “It could, however, cover the typical needs of a diabetes patient who eats three meals a day,” Fussenegger says. He explains that insulin remains in the vesicles for a long time, even if a person doesn’t eat for more than four hours. “There’s no depletion or unintentional discharge taking place.”

As a proof of concept only, clinical application is a long way off, but it shows that genetic networks can be controlled by mechanical stimuli such as sound waves. Whether this principle will ever be put to practical use depends on whether a pharmaceutical company is interested in doing so. It could, after all, be applied broadly: the system works not only with insulin, but with any protein that lends itself to therapeutic use.

Source: ETH Zurich

Categories : Medical Research & Technology Metabolic DisordersTags :

This Open-source Autoinjector Could Be Made for a Tenth of the Price of Commercial Ones

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Research team led by Joshua Pearce has developed a new 3-D printed, completely open-source autoinjector for a tenth of the cost of a commercially purchased product. (Photo by Anjutha Selvaraj)

A new study published in PLOS One describes the development of a spring-driven autoinjector for the delivery of insulin and other medications. This device, made from a combination of 3D-printed and commercially available parts, could cost less than $7 to make while a store-bought version is closer to $70.

Sir Frederick Banting was an inspiration for a new open source self-administering drug delivery device. Long before open source was an option or even a concept, the now-celebrated former University of Western Ontario lecturer refused to patent insulin because he wanted it to be inexpensive and widely available for the betterment of all.

A century after Banting won the Nobel Prize for his discovery, Western researchers led by engineering and Ivey Business School professor Joshua Pearce has developed a new 3D printed, completely open-source autoinjector – a device designed to deliver a single dose of medicine – for a tenth of the cost of a commercially purchased product.

“I think of this device, like so much of what we’re doing here at Western, very much as following the golden rule: do unto others as you would have them do unto you,” said Pearce. “It makes the world slightly better to have an open-source version of an autoinjector, especially for people who don’t have access or the financial means to purchase a proprietary one.”

Autoinjectors are used all over the world by health care practitioners, patients and parents (for children under 12) to inject insulin into people with diabetes. Other chronic conditions such as psoriasis, multiple sclerosis and rheumatoid arthritis can also be treated using an autoinjector. The device is also essential during emergency conditions for migraine, anaphylaxis and status epilepticus patients, as well.

Pearce, along with research assistant Anjutha Selvaraj and post-doctoral associate Apoorv Kulkarni, have created the new open-source autoinjector to make the device – considered more reliable and easier to operate than a simple syringe for self-administering medications into the body – an equitable alternative to the more expensive options.

Studies show self-administration of medications by patients improves compliance and comfort and empowers patients as they are actively involved in their personal care. It also allows patients to avoid time-consuming and costly visits to the hospital, which is a bonus for overburdened health care systems.

And, as with all open-source hardware, there is money to be made as the digitally replicable device enables low-cost distributed manufacturing. All materials, designs and assembly instructions are also detailed in the new study, and the effectiveness of the autoinjector is tested against the current standard (ISO 11608-1:2022) for needle-based injection systems. It is released with an open source hardware license. Companies wishing to commercialise the device will still need to meet their own local regulatory requirements.

“Does this design make it possible for other people to commercialise it anywhere in the world? Yes, it does,” said Pearce. “But more importantly, it means we can really target isolated communities, whether they’re in northern Canada, Africa or anywhere in else in the world, and improve health care access for everyone.”

Source: University of Western Ontario

Categories : Metabolic DisordersTags :

The Body’s Safety Valve Against Insulin Shock

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Novolog insulin pen. Photo by Dennis Klicker on Unsplash

Insulin is an important treatment for people with type 1 or 2 diabetes, but excessive insulin can cause hypoglycaemia, leading to convulsions, coma and possibly death – a collection of conditions that defines insulin shock.

In a new study published in Cell Metabolism, a team of scientists at the University of California San Diego School of Medicine, with colleagues elsewhere, describe a key component in the mechanism that regulates against excessive insulin.

“Although insulin is one of the most essential hormones, whose insufficiency can result in death, too much insulin can also be deadly,” said senior study author Professor Michael Karin, PhD, at UC San Diego School of Medicine.

In the new study, Karin, first author Li Gu, PhD, a postdoctoral scholar in Karin’s lab, and colleagues describe “the body’s natural defence or safety valve” that reduces the risk of insulin shock.

That valve is a metabolic enzyme called fructose-1,6-bisphosphate phosphatase or FBP1, which acts to control gluconeogenesis, a process in which the liver synthesises glucose, during sleep and secretes it to maintain steady supply of glucose in the bloodstream.

Some antidiabetic drugs, such as metformin, inhibit gluconeogenesis but without apparent ill effect. Children born with a rare, genetic disorder in which they do not produce sufficient FBP1 can also remain healthy and live long lives.

But in other cases, when the body is starved for glucose or carbohydrates, an FBP1 deficiency can result in severe hypoglycaemia, leading to convulsions, coma and possibly death.

Compounding and confounding the problem, FPB1 deficiency combined with glucose starvation produces adverse effects unrelated to gluconeogenesis, such as an enlarged, fatty liver, mild liver damage and elevated blood lipids or fats.

To better understand the roles of FBP1, researchers created a mouse model with liver specific FBP1 deficiency, accurately mimicking the human condition. Like FBP1-deficient children, the mice appeared normal and healthy until fasted, which quickly resulted in the severe hypoglycaemia and the liver abnormalities and hyperlipidaemia described above.

Gu and her colleagues discovered that FBP1 had multiple roles. Beyond playing a part in the conversion of fructose to glucose, FBP1 had a second non-enzymatic but critical function: It inhibited the protein kinase AKT, which is the primary conduit of insulin activity.

“Basically, FBP1 keeps AKT in check and guards against insulin hyper-responsiveness, hypoglycaemic shock and acute fatty liver disease,” said first author Gu.

Working with Yahui Zhu, a vising scientist from Chongqing University in China and second author of the study, Gu developed a peptide (a string of amino acids) derived from FBP1 that disrupted the association of FBP1 with AKT and another protein that inactivates AKT.

“This peptide works like an insulin mimetic, activating AKT,” said Karin. “When injected into mice that have been rendered insulin resistant, a highly common pre-diabetic condition, due to prolonged consumption of high-fat diet, the peptide (nicknamed E7) can reverse insulin resistance and restore normal glycaemic control.”

Karin said the researchers would like to further develop E7 as a clinically useful alternative to insulin “because we have every reason to believe that it is unlikely to cause insulin shock.”

Source: University of California – San Diego

Categories : Medical Industry Metabolic DisordersTags :

Biden Urges Drug Companies to Join in Insulin US Price Cuts

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Photo by Dennis Klicker on Unsplash

Following pharmaceutical company Eli Lilly’s much-lauded move to cut US prices for its insulin products, US President Joe Biden is calling on other drugmakers to make similar reductions for the vital medication.

According to Euronews, Lilly is directly slashing its insulin prices by about 70%, since many patients cannot access discounts, and is capping consumer costs at US$35 (R635) a month.

Biden is driving a push for cheaper insulin, signing a law that capped insulin at US$35 a month for senior citizens on Medicare, and urged companies to lower prices on their own. “For far too long, American families have been crushed by drug costs many times higher than what people in other countries are charged for the same prescriptions,” Biden said.

“Insulin costs less than US$10 to make, but Americans are sometimes forced to pay over US$300 for it. It’s flat wrong”.

Biden has called for a national cap on insulin prices, but his current Act does not extend to that.

A Lilly press release revealed that the price of Humalog® (insulin lispro injection) 100 units/mL (Lilly’s most commonly prescribed insulin) and Humulin® (insulin human) injection 100 units/mL by would be cut by 70%. This price change would take effect around the end 2023. Lilly also said it would cut the price for the generic Lispro to US$25 a vial starting in May. In South Africa, a Humulin® 10mL vial costs R525.28, or US$28.08, according to Health-e’s medicine price registry.

Lilly CEO David Ricks said his company was bringing the changes as not all patients could benefit through discounts through insurers or pharmacy benefit managers.

“We are driving for change in repricing older insulins, but we know that 7 out of 10 Americans don’t use Lilly insulin. We are calling on policymakers, employers and others to join us in making insulin more affordable,” said Ricks. “For the past century, Lilly has focused on inventing new and improved insulins and other medicines that address the impact of diabetes and improve patient outcomes. Our work to discover new and better treatments is far from over. We won’t stop until all people with diabetes are in control of their disease and can get the insulin they need.”

Since insurers and pharmacies will take a while to implement the price cuts, Lilly will immediately cap monthly out-of-pocket costs at $35 for people who are not covered by Medicare’s prescription drug programme.