Diabetes Messengers

The immune system is not immune to mistakes. In type 1 diabetes, it wrongly identifies beta cells (large, green) within the pancreas as pathogens. It attacks and destroys these cells, while leaving other cells in the pancreas (small, blue) untouched. Beta cells produce a hormone, called insulin, which controls the levels of sugar in the blood. Insulin stimulates our body’s cells to absorb sugar by opening up shuttles, called transport proteins (red), on the cells’ edge. Diabetic patients can manage their sugar levels with injections of insulin, but may suffer complications. If doctors could diagnose and treat the condition earlier, they could reduce such complications and extend a patient’s life. Scientists at the MRC’s Clinical Sciences Centre have shown that when beta cells die, they release large quantities of a molecule, called microRNA 375, into the blood. A simple blood test could detect this molecule years before symptoms develop.

Find out more about this study, and the Clinical Sciences Centre’s research on pancreatic cells.

Written by Deborah Oakley

Image produced from work by Mathieu Latreille The MRC’s Clinical Sciences Centre Copyright held by original author Research published in Journal of Molecular Medicine, May 2015 You can also follow BPoD on Twitter and Facebook

Diabetes in a Dish
With NIH grant, UC San Diego researchers hope to build bits of miniature pancreas

Although type 1 diabetes can be controlled with insulin injections and lifestyle modifications, major advances in treating the disease have not been made in more than two decades and there remain fundamental gaps in what is understood about its causes and how to halt its progression.

With a 5-year, $4-million grant from the National Institutes of Health, researchers at University of California, San Diego School of Medicine and bioengineers at UC San Diego Jacobs School of Engineering, with colleagues at UC Irvine and Washington University in St. Louis hope to change this.

The team’s goal is to bioengineer a miniature pancreas in a dish, not the whole pancreas but the organ’s irregularly shaped patches – called Islets of Langerhans – that regulate the body’s blood sugar levels.

“The bottleneck to new cures for type 1 diabetes is that we don’t have a way to study human beta cells outside of the human body,” said Maike Sander, MD, professor in  the departments of Pediatrics and Cellular and Molecular Medicine and director of the Pediatric Diabetes Research Center at UC San Diego and Rady Children’s Hospital-San Diego. “If we are successful, we will for the first time be able to study the events that trigger beta cell destruction.”

Beta cells in islets secrete the hormone insulin. In patients with type 1 diabetes, the beta cells are destroyed and the body loses its ability to regulate blood sugar levels. Researchers, however, are unsure of the mechanism by which beta cells are lost. Some researchers believe that the disease may be triggered by beta cell apoptosis (self-destruction); others believe that the body’s immune system initiates attacks on these cells.

To actually bioengineer the pancreas’ endocrine system, researchers plan to induce human stem cells to develop into beta cells and alpha cells, as well as other cells in the islet that produce hormones important for controlling blood sugar levels. These cells will then be co-mingled with cells that make blood vessels and the cellular mass will be placed within a collagen matrix mimicking the pancreas. The matrix was developed by Karen Christman, PhD, associate professor of bioengineering at the Jacobs School of Engineering.

“Our previous work with heart disease has shown that organ-specific matrices help to create more mature heart cells in a dish,” Christman said. “I am really excited to apply the technology to diabetes research.”

If the pancreatic islets can be successfully bioengineered, researchers could conduct mechanistic studies of beta cell maturation, replication, reprogramming, failure and survival. They say new drug therapies could be tested in the 3D culture. It would also be possible to compare beta cells from people with and without the disease to better understand the disease’s genetic component. Such work might eventually lead to treatments for protecting or replacing beta cells in patients.

30 November 2013

Plan Beta

For Type 1 diabetes sufferers, eating a chocolate bar can be deadly. This is because they lack a protein called insulin, which removes sugar from the blood preventing dangerously high concentrations occurring. The irreversible destruction of the pancreas’ beta cells that produce insulin is to blame, and often means enduring a lifetime of injections to keep sugar levels in check. However, switching off one particular gene can transform different cells into these vital insulin factories. With this gene inactivated, new beta cells (here coloured green) have begun to re-emerge, only four days after they were completely eliminated from this mouse pancreas. In the midst of a global diabetes epidemic that has seen the number of sufferers rise seven-fold over the last 20 years, this new avenue of exploration for potential treatment methods is most welcome.

Written by Jan Piotrowski

Image by Monica Courtney and others
University of Nice-Sophia Antipolis, France
Originally published under a creative commons attribution licence
Research published in PLOS Genetics, October 2013
Stem Cell-Derived Beta Cells Under Skin Replace Insulin

Scientists at University of California, San Diego School of Medicine and Sanford-Burnham Medical Research Institute have shown that by encapsulating immature pancreatic cells derived from human embryonic stem cells (hESC), and implanting them under the skin of diabetic mouse models, sufficient insulin is produced to maintain glucose levels without unwanted potential trade-offs of the technology.

The research, published online in Stem Cell Research, suggests that encapsulated hESC-derived insulin-producing cells may be an effective and safe cell replacement therapy for insulin dependent-diabetes.

“Our study critically evaluates some of the potential pitfalls of using stem cells to treat insulin dependent-diabetes,” said Pamela Itkin-Ansari, PhD, assistant project scientist in the UC San Diego Department of Pediatrics and adjunct assistant professor in Development, Aging and Regenerative program at Sanford-Burnham.

“We have shown that encapsulated hESC-derived insulin-producing cells are able to produce insulin in response to elevated glucose without an increase in the mass or their escape from the capsule,” said Itkin-Ansari. “These results are important because it means that the encapsulated cells are both fully functional and retrievable.”

Previous attempts to replace insulin producing cells, called beta cells, have met with significant challenges. For example, researchers have tried treating diabetics with mature beta cells, but because these cells are fragile and scarce, the method is fraught with problems. Moreover, since the cells come from organ donors, they may be recognized as foreign by the recipient’s immune system – requiring patients to take immunosuppressive drugs to prevent their immune system from attacking the donor’s cells, ultimately leaving patients vulnerable to infections, tumors and other adverse events.

Encapsulation technology was developed to protect donor cells from exposure to the immune system – and has proven extremely successful in preclinical studies.

Itkin-Ansari and her research team previously made an important contribution to the encapsulation approach by showing that pancreatic islet progenitor cells are an optimal cell type for encapsulation. They found that progenitor cells were more robust than mature beta cells to encapsulate, and while encapsulated, they matured into insulin-producing cells that secreted insulin only when needed.

In the study, Itkin-Ansari and her team used bioluminescent imaging to determine if encapsulated cells stay in the capsule after implantation.

“We were thrilled to see that the cells remained fully encapsulated for up to 150 days, the longest period tested,” said Itkin-Ansari. “Equally important is that we show that the progenitor cells develop glucose-responsiveness without a significant change in mass – meaning they don’t outgrow their capsule.”

Next steps for the development of the approach will be to figure out the size of the capsule required to house the number of progenitor beta cells needed to respond to glucose in humans.

“And of course we want to learn how long a capsule will function once implanted,” said Itkin-Ansari. “Given these goals and continued successful results, I expect to see the technology become a treatment option for patients with insulin dependent-diabetes.”

Patching into diabetes could start changing lives

Managing diabetes can be a challenge at the best of times. Monitoring blood sugar levels, taking insulin injections at just the right time. That may be about to change thanks to a tiny patch.

The group of Dr. Zhen Gu at the University of North Carolina have developed a patch that not only senses changes in blood sugar levels, but administers insulin and blood-glucose sensing enzymes to track levels and stop spikes in blood sugar levels.

Source: University of North Carolina

The patch, made from biocompatible materials, has 100 tiny needles and imitates Beta cells, which generate and store insulin. The patch acts as a proxy to these cells and takes over the monitoring of blood sugar and insulin levels.

The patch could be a game-changer for the more than 387 million people worldwide living with diabetes.

ViaCyte on the Rise: Buys BetaLogics IP & First Diabetes Trial Data

ViaCyte on the Rise: Buys BetaLogics IP & First Diabetes Trial Data

Clinical research on Type I Diabetes is one of the most exciting and promising areas of stem cells and regenerative medicine for human disease.

Two of the coolest companies out there in this arena have been ViaCyte and BetaLogics (owned by J&J). For more on ViaCyte see my interview with President and CEO Paul Laikind from 2015.

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VC-01 post-implant

Today brings great news for ViaCyte on two fronts.…

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A Molecular Link Between Type 2 Diabetes and Some Psychiatric Disorders

New research in The FASEB Journal suggests that prevalent protein found in schizophrenia also plays a direct role in the function of pancreatic beta cells, which produce insulin to maintain blood sugar levels.

There may be a genetic connection between some mental health disorders and type 2 diabetes. In a new report appearing in the February 2016 issue of The FASEB Journal, scientists show that a gene called “DISC1,” which is believed to play a role in mental health disorders, such as schizophrenia, bipolar disorder and some forms of depression, influences the function of pancreatic beta cells which produce insulin to maintain normal blood glucose levels.

“Studies exploring the biology of disease have increasingly identified the involvement of unanticipated proteins–DISC1 fits this category,” said Rita Bortell, Ph.D., a researcher involved in the work from the Diabetes Center of Excellence at the Universityof Massachusetts Medical School in Worcester, Massachusetts. “Our hope is that the association we’ve found linking disrupted DISC1 to both diabetes and psychiatric disorders may uncover mechanisms to improve therapies, even preventative ones, to alleviate suffering caused by both illnesses which are extraordinarily costly, very common, often quite debilitating.”

“Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic β-cell function via glycogen synthase kinase-3β” by Agata Jurczyk, Anetta Nowosielska, Natalia Przewozniak, Ken-Edwin Aryee, Philip DiIorio, David Blodgett, Chaoxing Yang, Martha Campbell-Thompson, Mark Atkinson, Leonard Shultz, Ann Rittenhouse, David Harlan, Dale Greiner, and Rita Bortell in FASEB Journal. Published online February 2016 doi:10.1096/fj.15-279810

Hope for Type 1 Diabetics

Some good news for those with Type 1 Diabetes (insulin-dependent).  This form of Diabetes, which usually gets diagnosed during childhood and is dependent on life-long injections of insulin, occurs when the immune system destroys pancreatic beta cells and the body stops producing its own insulin. 

Insulin production

New technology has enabled researchers to detect far lower levels of insulin and have found that 73% of diabetics tested had working beta cells producing low levels of insulin regardless of how long they’ve had the disease.  Possible reasons include:

  • Some cells being immune to attack
  • New cells regenerating

This opens up the possibility to focus on regeneration of beta cells in future medical research, or even the link between nutrition/environment and auto-immune disease.

Genetic markers

German researchers found 2 genetic markers that predicts whether children will develop Type 1 Diabetes - DR3/DR4-DQ8.  I would like to emphasize that this doesn’t mean you WILL develop Type 1 Diabetes.  It just makes it more likely if all the right triggers are present.  In future this could make it easier for healthcare practitioners to identify those at risk and develop a lifestyle plan to avoid triggers.

Read more:

Most Type 1’s still producing Insulin

Blood Test to predict Type 1 Diabetes

Developed by researchers at Harvard University, the innovative new technique involves essentially recreating the formation process of beta cells, which are located in the pancreas and secrete insulin. By stimulating certain genes in a certain order, the Boston Globe reports that scientists were able to charm embryonic stem cells – and even altered skin cells – into becoming beta cells.

The whole process took 15 years of work, but now lead researcher Doug Melton says the team can create hundreds of millions of these makeshift beta cells, and they’re hoping to transplant them into humans starting in the next few years. 

“We are reporting the ability to make hundreds of millions of cells — the cell that can read the amount of sugar in the blood which appears following a meal and then squirts out or secretes just the right amount of insulin,”Melton told NPR.

There are 29.1 million people in the United States believed to have diabetes, according to statistics by the Centers for Disease Control and Prevention dating back to 2012. That’s 9.3 percent of the entire population. 

Currently, diabetes patients must rely on insulin shots to keep their blood-sugar levels stable, a process that involves continual monitoring and attentiveness. Failure to efficiently control these levels can cause some patients to go blind, suffer from nerve damage and heart attacks, and even lose limbs. If Melton’s beta cell creation process can be successfully applied to humans, it could eliminate the need for such constant check-ups, since the cells would be doing all the monitoring. 

Already, there are positive signs moving forward: the transplanted cells have worked wonders on mice, quickly stabilizing their insulin levels. 

“We can cure their diabetes right away — in less than 10 days,” Melton said to NPR. “This finding provides a kind of unprecedented cell source that could be used for cell transplantation therapy in diabetes.”

With mice successfully treated, the team is now working with a scientist in Chicago to put cells into primates, the Globe reported. 

Even so, significant obstacles remain, particularly for those who have Type 1 diabetes. With this particular form of the disease, the human immune system actually targets and destroys insulin-producing beta cells in the pancreas, so Melton’s team is looking into encasing cells inside of a protective shell in order to ensure their safety. 

Another hurdle is political, since many are against tinkering with human embryonic stem cells on the grounds that research wipes out human embryos. As a result, scientists are also trying to recreate their work on other types of stem cells. 

Regardless, the research – formally published in the Cell journal this week – is being welcomed with open arms. 

“It’s a huge landmark paper. I would say it’s bigger than the discovery of insulin,” Jose Olberholzer, a professor of bioengineering at the University of Illinois, told NPR. “The discovery of insulin was important and certainly saved millions of people, but it just allowed patients to survive but not really to have a normal life. The finding of Doug Melton would really allow to offer them really something what I would call a functional cure. You know, they really wouldn’t feel anymore being diabetic if they got a transplant with those kind of cells.”


Ru El's Running 090 : Hey Lonnie! | How Many Symptoms Confirm Diabetes?

Ru El’s Running 090 : Hey Lonnie! | How Many Symptoms Confirm Diabetes?

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Lonnie Beauchamp and Ru El finally get together to discuss the question “How many symptoms confirm diabetes?”

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