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General => Science => Topic started by: Recusant on May 06, 2024, 03:31:46 AM

Title: Oral Insulin
Post by: Recusant on May 06, 2024, 03:31:46 AM
This really looks promising. Will probably be expensive at first, once it's approved.

"Nanotech opens door to future of insulin medication" | Phys.org (https://phys.org/news/2024-05-nanotech-door-future-insulin-medication.html)

QuoteAn international team, led by researchers from Australia, have developed a system using nanotechnology that could allow people with diabetes to take oral insulin in the future. The researchers say the new insulin could be eaten by taking a tablet or even embedded within a piece of chocolate.

The new nano carrier, tested in mice, rats and baboon animal models, could help people with diabetes avoid side-effects linked to insulin injections such as hypoglycemia (a low blood sugar event, when too much insulin has been injected).

These animal studies have shown that the greatest strength of the nano-scale material is that it can react to the body's blood sugar levels. The coating dissolves and releases the insulin when there is a high concentration of blood sugar and importantly does not release the insulin in low blood sugar environments.

The new oral insulin uses a type of nano-scale material that is 1/10,000th the width of a human hair. The material acts similarly to acid resistant coating on tablets, which protects it from being destroyed by stomach acid. But this new coating instead surrounds individual insulin molecules and becomes a "nano carrier"—acting like a courier to ferry insulin molecules in the body to the places it needs to act.

[Continues . . . (https://phys.org/news/2024-05-nanotech-door-future-insulin-medication.html)]

The paper is open access--

"Oral nanotherapeutic formulation of insulin with reduced episodes of hypoglycaemia" | Nature Nanotechnology (https://www.nature.com/articles/s41565-023-01565-2)

QuoteAbstract:

Injectable insulin is an extensively used medication with potential life-threatening hypoglycaemic events. Here we report on insulin-conjugated silver sulfide quantum dots coated with a chitosan/glucose polymer to produce a responsive oral insulin nanoformulation.

This formulation is pH responsive, is insoluble in acidic environments and shows increased absorption in human duodenum explants and Caenorhabditis elegans at neutral pH. The formulation is sensitive to glucosidase enzymes to trigger insulin release.

It is found that the formulation distributes to the liver in mice and rats after oral administration and promotes a dose-dependent reduction in blood glucose without promoting hypoglycaemia or weight gain in diabetic rodents. Non-diabetic baboons also show a dose-dependent reduction in blood glucose. No biochemical or haematological toxicity or adverse events were observed in mice, rats and non-human primates. The formulation demonstrates the potential to orally control blood glucose without hypoglycaemic episodes.
Title: Re: Oral Insulin
Post by: Icarus on May 06, 2024, 10:43:23 PM
Welcome news for insulin dependent people.
Title: Re: Oral Insulin
Post by: Tank on May 07, 2024, 10:49:43 AM
Very interesting.

Being insulin dependent type 2 is a real pain. I have now got a 24/7 sensor in my arm and it has been an absolute game changer over the last 3 months. Because the sensor is embedded under the skin with it's control-unit/transmitter stuck on the outside I don't have to do an individual pin prick on my finger anymore. That is a vast improvement. The system sends around 90 readings a day to my phone. There is no way I could do that with my old blood prick system my fingers would be a bloody mess!

This is the daily view.

(https://imageshack.com/i/pnhokgk1p)
Title: Re: Oral Insulin
Post by: Icarus on May 08, 2024, 01:22:01 AM
Three cheers for medical science.
Title: Re: Oral Insulin
Post by: Tank on May 08, 2024, 07:31:04 AM
Hear hear! No question I would have died of sepsis if it hadn't been for antibiotics.
Title: Re: Oral Insulin
Post by: Recusant on March 26, 2026, 02:53:10 AM
A different route for oral insulin--this one may be more likely to get to the public than the nano tech in the OP.

"Insulin pills may soon replace daily injections" | ScienceDaily (https://www.sciencedaily.com/releases/2026/03/260324024302.htm)

QuoteFor more than 100 years, scientists have pursued the idea of insulin in pill form, often described as a "dream" treatment for diabetes. The challenge has been the body itself. Enzymes in the digestive system break down insulin before it can work, and the intestine lacks a natural way to absorb it into the bloodstream. As a result, many patients still depend on daily injections, which can take a toll on their quality of life.

A team at Kumamoto University, led by Associate Professor Shingo Ito, has now developed a promising solution. Their approach uses a cyclic peptide that can pass through the small intestine, known as the DNP peptide. This platform allows insulin to be delivered orally in a way that was not previously possible.

To make this work, the researchers designed two different methods to help insulin cross the intestinal barrier:

Mixing method (interaction-based): The team combined a modified "D-DNP-V peptide" with zinc-stabilized insulin hexamers. When given orally to several diabetes models, including chemically induced (STZ mice) and genetic (Kuma mice) models, this mixture quickly brought blood sugar levels down to normal. Stable glucose control was maintained with once-daily dosing for three consecutive days.

Conjugation method (covalent-based): Using click chemistry, the researchers attached the DNP peptide directly to insulin, creating a "DNP-insulin conjugate." This version lowered blood sugar just as effectively as the mixing method, confirming that the peptide actively helps transport insulin through the intestine.

One of the biggest obstacles for oral insulin has been the need for extremely high doses, sometimes more than ten times higher than injections. This new platform significantly reduces that requirement. It achieved a pharmacological bioavailability of about 33-41% compared to subcutaneous injection. That level of efficiency suggests oral insulin could become far more practical for real-world use.

[Continues . . . (https://www.sciencedaily.com/releases/2026/03/260324024302.htm)]


The paper (https://pubmed.ncbi.nlm.nih.gov/41284288/) is behind a paywall.

QuoteAbstract:

Oral administration of protein therapeutics, such as insulin, is hindered by enzymatic degradation and poor intestinal permeability. To overcome these barriers, we present a peptide-based delivery platform that uses a DNP peptide that is permeable in the small intestine.

We engineered DNP-V, a modular carrier peptide, fused to an insulin-interacting peptide. We demonstrated that the coadministration of DNP-V with zinc-stabilized insulin hexamers in diabetic mice enables a rapid, robust, and sustained reduction in blood glucose levels to near-normal levels. This effect was reproducible across multiple diabetic models, achieving significant suppression of the initial postprandial glucose surge with once-daily oral dosing.

This platform can be easily applied to long-acting insulin analogs, allowing for oral delivery without the need for complex preparation changes. Additionally, covalent conjugation of DNP peptides to insulin via click chemistry yielded stable insulin conjugates that significantly enhanced intestinal absorption and produced comparable oral glucose-lowering effects. This confirms the direct contribution of the carriers to the absorption.

These findings establish DNP peptides as versatile, modular platforms for the oral delivery of macromolecular therapeutics. As long as an appropriate conjugatable partner is available, this technology can simply and effectively convert injectable biopharmaceuticals into orally administrable forms, offering a promising path to practical, patient-friendly oral therapies.

Title: Re: Oral Insulin
Post by: Recusant on May 23, 2026, 05:08:22 AM
Though this isn't about insulin as a medicine exactly, it more or less fits in this thread. I don't know that any of us here will get to enjoy the eventual advances in stem cell therapy, but there seems to be some promise there.

"Stem cells have potent potential for diabetes treatment" | The Conversation (https://theconversation.com/stem-cells-have-potent-potential-for-diabetes-treatment-280003)

QuoteHumans have around 30 trillion cells in our adult bodies. Amazingly, each of these cells came from a handful of about 100 stem cells in the earliest days of development. The ability of these embryonic stem cells to turn into any cell type makes them pluripotent — something that researchers are harnessing in science and medicine today.

The use of human embryonic stem cells in research began in 1998, when several human embryos were donated from couples undergoing in vitro fertilization. From these embryos, scientists generated a virtually unlimited supply of pluripotent cells. Almost 30 years later, these embryonic stem cell lines are still used in many research labs today.

Another milestone in stem cell research came in 2007, when two labs — led by Shinya Yamanaka at the University of Kyoto in Japan and by James Thomson at the University of Wisconsin-Madison in the United States — separately published papers on how they had reprogrammed mature cells (like skin cells) back to a stem cell-like pluripotent state.

These are known as induced pluripotent stem cells. Their main benefit is that they carry a person's own DNA, enabling more personalized disease-modelling and therapies.

In our research lab, we use embryonic stem cells to generate insulin-producing beta cells — the cell type that is destroyed by the immune system in people with Type 1 diabetes. The loss of these insulin-producing beta cells leaves patients dependent on insulin injections to control blood sugar levels and prevent severe complications like blood vessel and nerve damage.

Insulin therapy does not relieve the emotional load of living with Type 1 diabetes. It also does not fully replace the dynamic function of the body's own beta cells, so many people with Type 1 diabetes still experience long-term health problems.

To overcome this, researchers are making lab grown stem cell-derived beta cells to try to restore the body's ability to produce insulin. Recent clinical trials have shown promising results of transplanting these cells into individuals with Type 1 diabetes:

• Vertex Pharmaceuticals transplanted beta cells derived from embryonic stem cells into 12 patients with Type 1 diabetes, and 10 (83 per cent) were able to stop insulin injections within six months.

• A research team from China reprogrammed a Type 1 diabetes patient's fat cells into induced pluripotent stem cells, turned the induced pluripotent stem cells into beta cells, and then transplanted them under the patient's abdominal muscle. Remarkably, the recipient became insulin-independent 75 days after surgery and remained so for at least 12 months.

These early trials show that stem cell-derived beta cells can survive, mature and function after transplantation into patients. But challenges remain, including ensuring cells fully develop into the cell type of interest, producing cells safely and efficiently at large scales and preventing immune rejection.

[. . .]

Stem cells offer an extraordinary toolkit for scientific research and medicine. Researchers are getting better at turning these pluripotent cells into specialized tissues and the first successful clinical trials are already here. However, these therapies are still experimental and not yet approved by Health Canada or the Food and Drug Administration in the United States.

Patients should be cautious of unapproved stem cell therapies and always consult their health-care professional before joining approved clinical trials. The progress made so far brings real hope that future stem cell therapies could improve the lives of people living with chronic diseases.

[Full article. (https://theconversation.com/stem-cells-have-potent-potential-for-diabetes-treatment-280003)]