Tag Archives: Insulin

“Reconnecting” metabolism in insulin-producing cells may help the treatment of type 2 diabetes-health | Instant News

Researchers have discovered a previously unknown method by which pancreatic cells determine how much insulin they secrete.It could provide a promising new target to develop drugs to increase insulin production in diabetic patients Type 2 diabetes.

In two recently published papers Cell metabolismScientists at the University of Wisconsin-Madison and their colleagues pointed out that an overlooked enzyme called pyruvate kinase is the main way for pancreatic beta cells to sense sugar levels and release the right amount of insulin.

Through several proof-of-concept experiments conducted on rodent and human pancreatic cells, the research team found that drugs that stimulate pyruvate kinase not only increase insulin secretion, but also have other metabolic protective effects on the liver, muscles, and red blood cells. Research results indicate that activation of pyruvate kinase may be a new way to increase insulin secretion to fight type 2 diabetes, but more research is needed before any new treatments are available.

Matthew Merrins, professor of medicine at the University of Western Australia School of Medicine and School of Public Health, who is in charge of this work, said: “Too much insulin will lower blood sugar to dangerous levels, and too much insulin can lead to diabetes.” The question to ask is: How do nutrients such as glucose and amino acids open up the beta cells in the pancreas to release the right amount of insulin?”

This work is based on a careful analysis of the contradictory timing of key biochemical events, when it was generally understood how pancreatic beta cells respond to nutrients in the blood. The researchers pointed out a new and richer model to understand how to control this important process to resolve these contradictions.

For decades, scientists have believed that mitochondria, the energy generators in cells, trigger insulin secretion. This is a natural explanation, because mitochondria produce the high-energy molecule ATP, and in the process deplete the low-energy form of ATP, ADP. The decline in ADP stimulates calcium, the ultimate trigger for the release of stored insulin.

But time makes no sense. Mitochondria are most active when insulin secretion has already begun, not before. In addition, the mitochondria will stall before they exhaust enough ADP to trigger insulin secretion.

The clues to resolve these obvious paradoxes came from the study of cardiomyocytes in the 1980s. At the time, scientists discovered that pyruvate kinase (which converts sugar into energy and does not rely on mitochondria) may also severely deplete ADP. This process occurs near the ADP sensor protein involved in insulin release in the pancreas. Mellins’ team believes that perhaps the pancreas uses this proximity to fine-tune insulin release.

In the initial experiment, the researchers provided sugar and ADP to pancreatic cell slices containing pyruvate kinase. Enzymes engulf these two components and deplete ADP. Since pyruvate kinase is located near the ADP sensor protein that triggers insulin secretion, it has a great effect.

“This is one of the important concepts in our paper: The location of the metabolism is critical to its function,” Merrins said.

The researchers used mouse and human islets, clusters of cells that release insulin, to try to stimulate the activity of pyruvate kinase. The drug that activates this enzyme increases the release of insulin four-fold, but only if there is enough sugar around-pyruvate kinase cannot be forced to release too much insulin.

Merrins said: “Pyruvate kinase does not change the amount of fuel that enters the cell, but only changes the way the fuel is used.” “Drugs with active pyruvate kinase can strongly promote insulin secretion without causing excessive insulin release. Hypoglycemia.”

Overall, they found a more complicated way, which is evidence of how pancreatic beta cells decide when and how much insulin they release, similar to a two-stroke engine. In the first cycle, pyruvate kinase processes blood sugar and consumes ADP. Mitochondria maintain this process by supplying more material to pyruvate kinase, which can cause ADP levels to collapse and ultimately stimulate enough calcium to enter the cell to release insulin.

In the second cycle, mitochondria transition from adding material to pyruvate kinase to producing the high-energy molecule ATP, which is necessary for the complete release of insulin. Then, the process will reset.

In an accompanying study by colleagues at Yale University Mellins, researchers studied how pyruvate kinase activator affects the metabolism of healthy and obese rats. In a series of experiments, they found that activating pyruvate kinase can increase insulin secretion and insulin sensitivity, while improving glucose metabolism in the liver and red blood cells. This type of treatment may be useful for patients with type 2 diabetes, who cannot produce enough insulin and therefore have abnormal glucose metabolism.

Mellins said: “The therapeutic idea here is that we can rearrange our metabolism to trigger insulin secretion more effectively while improving the function of other organs.

(This story was posted from a telecommunications company feed and has not been modified.)

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Venomous Insulin From Conical Snails Appears Promising | Instant News

A malignant sea snail poison can change diabetes care and improve the quality of life for those suffering from diabetes, reports a new study. Nearly one hundred years after the discovery of insulin, an international research team has developed the smallest fully functional hormone version of a cone snail.

Mini-Insulin– The new version of insulin has the potential for human insulin in addition to the potential for rapid action of the insulin toxin produced by predatory cone snails.

“We now have the ability to make hybrid versions of insulin that work in humans and which also seem to have many positive attributes of cone snail insulin. That is an important step forward in our efforts to make diabetes care safer and more effective, “Danny Hung-Chieh Chou, Ph.D., assistant professor of biochemistry at the University of Utah Health and one of the authors of the relevant study told Phys.Org.

Key properties of Mini-Insulin:

  • Have similar in-vitro insulin signaling and in-vivo bioactivity similar to human insulin
  • It works faster than human insulin, which works the fastest
  • Rapid acting insulin will reduce the risk of hyperglycemia and other diabetes complications
  • This new insulin can also improve the performance of insulin pumps or artificial pancreas that release insulin into the body whenever needed
  • This can help individuals with diabetes to control their blood sugar levels more tightly and quickly

The research team found that new insulin derived from cone snail venom does not have a hinge compound that causes the human insulin hormone to clot so it can be stored in the pancreas. This aggregate must be simplified into individual molecules before they can start working on blood sugar.

They use structural biology and chemical drug techniques to isolate amino acids that help insulin slug bind to insulin receptors. The truncated version of the human insulin molecule is then made without the area that causes clots.

In testing in animals, new insulin insulin is bound to insulin receptors as strong as normal human insulin.

“Mini-insulin has tremendous potential. With only a few strategic changes, we have produced a strong and fast-acting molecular structure, which is the smallest and most fully active insulin to date. Because it is so small, it should be easy to synthesize, making it a prime candidate “for the development of a new generation of insulin therapy,” Chou told Phys.Org. Cone snail venom can change the treatment of diabetes Photo: Brett_Hondow, Pixabay


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Single-cell RNA-seq answers key questions in islet cell biology and diabetes research | Instant News

The pancreas is a stomach organ that produces digestive enzymes and hormones that regulate blood sugar levels. This hormone-producing function is localized on the island of Langerhans, which forms a group of various types of endocrine cells.

Among these are beta cells, which produce the hormone insulin which is needed to lower glucose levels (a type of sugar) in our blood, as well as alpha cells, which produce glucagon hormones whose job is to increase glucose levels in the blood.

Type 1 diabetes is a chronic disease where the immune system mistakenly attacks and destroys pancreatic insulin-producing beta cells. Regenerative medicine aims to replenish beta cell mass, and thus support and ultimately replace current insulin replacement therapy.

Changes in island composition, including lack of beta cell function and beta cell dedifference, also contribute to type II diabetes.

Therefore, a deeper understanding of the identity and crosstalk of various islet cell types leads to better characterization of both forms of diabetes and can contribute to the development of new therapeutic concepts.

Single cell transcriptomes are powerful techniques for characterizing cellular identity. Previously, CeMM researchers from the groups Christoph Bock and Stefan Kubicek at CeMM published the first single cell transcriptome from primary human pancreatic islet cells.

Advances in technology have enabled applications for the generation of global single cell atlase human and mouse transcript. Despite this progress, the single cell approach remains technologically challenging given the very small amount of RNA used in the experiment. Therefore, it is important to ensure the quality and purity of the resulting single cell transcriptome.

CeMM researchers in two laboratories who contributed unexpectedly identified high hormone expression in non-endocrine cell types, both in their own dataset and published single cell studies.

They set out to explain whether this would be the result of contamination by RNA molecules, for example from dying cells, and how they could be removed to obtain a more reliable dataset.

Such contamination appears to be present in RNA-seq single cell data from most tissues but is most visible on pancreatic islets. Islet endocrine cells are exclusively devoted to the production of a single hormone, and insulin in beta cells and glucagon in alpha cells is expressed to a higher level than a typical “household” gene.

Thus, the redistribution of these transcripts to other cell types is very clear. Based on these observations, their goal is to develop, validate and apply methods to experimentally determine and computationally eliminate the contamination.

In their investigation, the CeMM researchers used prickly cells of different cell types, both rat and human samples, which they added to their pancreatic islet samples. Importantly, the transcriptomes of these spike cells are fully characterized.

This enables them to internally and accurately control the level of RNA contamination in a single RNA-seq cell, providing that the human transcripts detected in mouse spike-in cells are contaminated RNA.

In this way, they found that the sample had a contamination rate of up to 20%, and was able to determine the contamination in each sample. They then developed a new bioinformatics approach to computationally eliminate contaminated readings from single cell transcriptomes.

Having now obtained the “decontamination” transcriptome, from which false signals have been removed, they proceed to characterize how cellular identities in different cell types respond to treatment with three different drugs.

They found that small molecular blockers of the FOXO1 transcription factor induced dedifferentiation of both alpha and beta cells.

Next, they studied artemeter, which has been found to reduce alpha cell function and can induce insulin production in both in vivo and in vitro studies. Effects of species-specific drug species and cell types.

In alpha cells, a small proportion of cells increase insulin expression and gain aspects of beta cell identity, both in rat and human samples. Importantly, the researchers found that in human beta cells, there was no significant change in insulin expression, whereas in mouse islands, beta cells reduced insulin expression and overall beta cell identity.

This study is the result of interdisciplinary collaboration from the laboratories of Stefan Kubicek and Christoph Bock at CeMM with Patrick Collombat at the Institute of Biology Valrose (France).

This is the first study to apply single cell sequencing to analyze dynamic drug responses in intact isolated tissue, which benefits from the high quantitative accuracy of the decontamination method.

Thus not only provides a new method for single cell decontamination and a very quantitative single cell analysis of drug responses in intact tissue, but also answers current questions that are important in islet cell biology and diabetes research. These findings could open up potential therapeutic avenues for treating type 1 diabetes in the future.


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