beta-cells

The latest mini-organ…

Engineered mini-stomachs produce insulin in mice

Researchers have spent decades trying to replace the insulin-producing pancreatic cells, called beta cells, that are lost in diabetes. Now a team of researchers, reporting Feb. 18, 2016 in Cell Stem Cell, have discovered that tissue from the lower stomach has the greatest potential to be reprogrammed into a beta-cell state. The researchers took samples of this tissue from mice and grew them into “mini-organs” that produced insulin when transplanted back into the animals. The mini-organs’ stem cells also continued to replenish the insulin-producing cell population, giving the tissue a sustainable regenerative boost.

Cell Stem Cell, Ariyachet et al.: “Reprogrammed stomach tissue as a renewable source of functional beta-cells for blood glucose regulation” http://dx.doi.org/10.1016/j.stem.2016.01.003

Caption: A section of the gastric mini-organ engineered to produce insulin-secreting cells, with immunofluorescent staining.  This image shows many induced insulin-producing cells (red) present in the mini-organ. Gastric stem and progenitor cells (green) are detected at the base of the glands. Cell nuclei labeled in blue. Credit: Chaiyaboot Ariyachet

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 LatreilleThe 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
Scientists discover new causes of diabetes

The research, published today in the journal Cell Metabolism, provides further insights on how the insulin-producing beta cells are formed in the pancreas. The team discovered that mutations in two specific genes which are important for development of the pancreas can cause the disease. These findings increase the number of known genetic causes of neonatal diabetes to 20. The study was funded by the Wellcome Trust, Diabetes UK, European Community’s Seventh Framework Programme, with some of the authors supported by the National Institute for Health Research (NIHR).

Dr Sarah Flanagan, lead author on the paper, said: “We are very proud to be able to give answers to the families involved on why their child has diabetes. Neonatal diabetes is diagnosed when a child is less than six months old, and some of these patients have added complications such as muscle weakness and learning difficulties with or without epilepsy.

“Our genetic discovery is critical to the advancement of knowledge on how insulin-producing beta cells are formed in the pancreas, which has implications for research into manipulating stem cells, which could one day lead to a cure.”

Dr Alasdair Rankin, Diabetes UK  Director of Research, said: “As well as shedding further light on the genetic causes of neonatal diabetes and providing answers for parents of children with this rare condition, this work helps us understand how the pancreas develops. Many people with diabetes can no longer make insulin and would benefit from therapies that replace the insulin producing beta cells of the pancreas. The results of this study are critical to bringing the day closer when this type of treatment is possible.”

Neonatal diabetes is caused by a change in a gene which affects insulin production. This means that levels of blood glucose (sugar) in the body rise dangerously high.

The Exeter team is the leading centre for neonatal diabetes having recruited over 1200 patients from more than 80 countries. This specific study focussed on 147 young people with neonatal diabetes, a rare condition which affects approximately 1 in 100,000 births. Following a systematic screen, 110 patients received a genetic diagnosis. For the remaining 37 patients, mutations in genes important for human pancreatic development were screened. Mutations were found in 11 patients, four of which were in one of two genes not previously known to cause neonatal diabetes (NKX2-2 and MNX1).

For many of the 121 (82%) patients who received a genetic diagnosis, knowing the cause of the diabetes will result in improved treatment, and for all the patients it will provide important information on risk of neonatal diabetes in future pregnancies. These patients also provide important scientific insights into pancreatic development.

sciencealert.com
Lab-grown human beta cells have blocked diabetes in mice for good
The first lab-grown, insulin-producing pancreatic cells *ever*.
By David Nield

For the first time, researchers have converted induced pluripotent stem cells - cells capable of turning into any other type of cell - into fully functioning pancreatic beta cells, and when transplanted into diabetic mice, they blocked the disease altogether.

While the process has yet to be tested in humans, the results are exciting, because the hallmark of diabetes is a loss of functioning beta cells. If we can figure out how to transplant new, healthy beta cells into diabetes patients, we’re looking at an actual cure, not just a treatment. “This discovery will enable us to produce potentially unlimited supplies of transplantable cells derived from a patient’s own cells,” lead researcher Ronald Evans told ABC News.

Diabetes, simply put, involves the loss of functioning beta cells in the pancreas: either these cells die (type I diabetes) or they don’t do as they’re told (type II diabetes), and in both cases, it leads to a lack of insulin to regulate the glucose levels in the blood. For a long time, scientists have been trying to replace these damaged or dead beta cells with healthy ones, and it finally looks as though they might have cracked it (in mice, at least).

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

Penicillin tactics revealed by scientists

Penicillin, the wonder drug discovered in 1928, works in ways that are still mysterious almost a century later. One of the oldest and most widely used antibiotics, it attacks enzymes that build the bacterial cell wall, a mesh that surrounds the bacterial membrane and gives the cells their integrity and shape. Once that wall is breached, bacteria die – allowing us to recover from infection.

That would be the end of the story, if resistance to penicillin and other antibiotics hadn’t emerged over recent decades as a serious threat to human health. While scientists continue to search for new antibiotics, they still don’t understand very much about how the old ones work.

Now Thomas Bernhardt, associate professor of microbiology and immunobiology at Harvard Medical School, and his colleagues have added another chapter to the story.

Their findings, published Dec. 4 in Cell, reveal how penicillin deals bacteria a devastating blow – which may lead to new ways to thwart drug resistance.

Hongbaek Cho, Tsuyoshi Uehara, Thomas G. Bernhardt. Beta-Lactam Antibiotics Induce a Lethal Malfunctioning of the Bacterial Cell Wall Synthesis Machinery. Cell, 2014; 159 (6): 1300 DOI: 10.1016/j.cell.2014.11.017

Bacteria in the plate on the left are susceptible to antibiotics but show resistance in the plate on the right.  Credit: James Gathany/CDC

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Amazing images reveal how kidneys develop

These incredible images have revealed insights into how the kidney develops from a tiny cluster of cells into a complex organ.

The time-lapse pictures of growing mouse kidneys are helping scientists to understand the early stages of development in mammals.

They identified a key molecule called beta-catenin that instructs cells to form specialised structures within the kidney. These structures – called nephrons –are responsible for filtering waste products from the blood to generate urine.

If nephrons don’t work properly, it can cause a wide range of health problems — from abnormal water and salt loss, to dangerously high blood pressure. The findings will help scientists to grow nephrons in the lab that can be used to study how kidneys function.

Using the time-lapse technique also means that the same mice can be studied over time, at different developmental stages. This significantly reduces the number of animals needed for this type of research.

The research was funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research.

Read more

Images credit: Dr Nils Lindstromm University of Edinburgh

When Bacteria Invade…

Despite therapeutic advances, mortality rates for neonatal meningitis have remained the same over the last two decades. Addressing this requires better understanding of how the disease is caused at a cellular and molecular level. Here we see the re-distribution of the protein beta-catenin (blue) in brain endothelial cells after infection by the bacteria Escherichia coli K1. This bacterium (the small, rod-like cells seen in the grayscale image) has been shown to cause neonatal meningitis.

Led by principal investigator Prasadarao Nemani, PhD, researchers in the Microbial Pathogenesis Research Lab at Children’s Hospital Los Angeles generated this image to better understand the cellular and molecular events that occur when these bacteria pass through the blood-brain barrier as occurs in cases of neonatal meningitis. Beta-catenin helps coordinate adhesion between cells and, in cases of neonatal meningitis, the adhesion between brain endothelial cells is disrupted, leading to brain edema or swelling where fluid accumulates in the brain.

“This helped us identify that re-distribution of beta-catenin helps the bacteria invade the brain endothelium and may serve as a critical step in causing neonatal meningitis,” say Subramanian Krishnan, post-doctoral fellow at Children’s Hospital Los Angeles, who was first author on the study published in Cellular Microbiology.

Image courtesy of Subramanian Krishnan, Prasadarao Nemani, PhD, and Esteban Fernandez, PhD, The Saban Research Institute, Children’s Hospital Los Angeles.

Boosting A Natural Protection Against Alzheimer’s Disease
Combining investigational therapy with gene variant may reduce dangers from debilitating brain plaques

Researchers at the University of California, San Diego School of Medicine have identified a gene variant that may be used to predict people most likely to respond to an investigational therapy under development for Alzheimer’s disease (AD). The study, published March 12 in Cell Stem Cell, is based on experiments with cultured neurons derived from adult stem cells.

“Our results suggest that certain gene variants allow us to reduce the amount of beta amyloid produced by neurons,” said senior author Lawrence Goldstein, PhD, director of UC San Diego Sanford Stem Cell Clinical Center and UC San Diego Stem Cell Program. “This is potentially significant for slowing the progression of Alzheimer’s disease.” AD is the most common cause of dementia in the United States, afflicting one in nine people age 65 and older.

The genetic risk factor investigated are variants of the SORL1 gene. The gene codes for a protein that affects the processing and subsequent accumulation of beta amyloid peptides, small bits of sticky protein that build up in the spaces between neurons. These plaques are linked to neuronal death and related dementia.

Previous studies have shown that certain variants of the SORL1 gene confer some protection from AD, while other variants are associated with about a 30 percent higher likelihood of developing the disease. Approximately one-third of the U.S. adult population is believed to carry the non-protective gene variants.

The study’s primary finding is that variants in the SORL1 gene may also be associated with how neurons respond to a natural compound in the brain that normally acts to protect nerve cell health. The protective compound, called BDNF, short for brain-derived neurotrophic factor, is currently being investigated as a potential therapy for a number of neurological diseases, including AD, because of its role in promoting neuronal survival.

For the study, UC San Diego researchers took skin cells from 13 people, seven of whom had AD and six of whom were healthy control subjects, and reprogrammed the skin cells into stem cells. These stem cells were coaxed to differentiate into neurons, and the neurons were cultured and then treated with BDNF.

The experiments revealed that neurons that carried disease-protective SORL1 variants responded to the therapy by reducing their baseline rate of beta amyloid peptide production by, on average, 20 percent. In contrast, the neurons carrying the risk variants of the gene, showed no change in baseline beta amyloid production.

“BDNF is found in everyone’s brain,” said first author Jessica Young, PhD, a postdoctoral fellow in the Goldstein laboratory. “What we found is that if you add more BDNF to neurons that carry a genetic risk factor for the disease, the neurons don’t respond. Those with the protective genetic profile do.”

“The value of this kind of stem cell study is that it lets us probe the uniquely human aspects of disease and identify how a person’s DNA might determine their drug response, in this case to a potential treatment for Alzheimer’s,” Young said. “Future clinical trials on BDNF should consider stratifying patients based on their SORL1 risk factor and likelihood of benefiting from the therapy.”

Pictured: amyloid plaque, courtesy Wellcome Images

(Image caption: Star–like glial cells in red surround alpha beta plaques in the cortex of a mouse with a model of Alzheimer’s Disease)

Experimental cancer drug restores memory in mouse model of Alzheimer’s

Memory and as well as connections between brain cells were restored in mice with a model of Alzheimer’s given an experimental cancer drug, Yale School of Medicine researchers reported in the journal Annals of Neurology.

The drug, AZD05030, developed by Astra Zeneca proved disappointing in treating solid tumors but appears to block damage triggered during the formation of amyloid-beta plaques, a hallmark of Alzheimer’s disease. The new study, funded by an innovative National Institutes of Health (NIH) program to test failed drugs on different diseases, has led to the launch of human trials to test the efficacy of AZD05030 in Alzheimer’s patients.

“With this treatment, cells under bombardment by beta amyloid plaques show restored synaptic connections and reduced inflammation, and the animal’s memory, which was lost during the course of the disease, comes back,” said Stephen M. Strittmatter, the Vincent Coates Professor of Neurology and senior author of the study.

In the last five years, scientists have developed a more complete understanding of the complex chain of events that leads to Alzheimer’s disease. The new drug blocks one of those molecular steps, activation of the enzyme FYN, which leads to the loss of synaptic connections between brain cells. Several other steps in the disease process have the potential to be targets for new drugs, Strittmatter said.

“The speed with which this compound moved to human trials validates our New Therapeutic Uses program model and serves our mission to deliver more treatments to more patients more quickly,” said Dr. Christopher P. Austin, director of NIH’s National Center for Advancing Translational Sciences (NCATS), which funded the work.

Yale’s Christopher H. van Dyck, a co-author of the paper, and Strittmatter have initiated a multi-site clinical trial to determine whether the drug can also benefit Alzheimer’s patients. For more information on this trial being directed by van Dyck, visit http://www.adcs.org/studies/Connect.aspx or https://clinicaltrials.gov (NCT02167256 and NCT01864655).

5kg of skin care right here! Carrots deliver high doses of vitamin A and beta carotene into the cells to promote skin healing, anti ageing and cell rejuvenation giving you that healthy golden glow. Carrots also assist in the prevention of acne, eczema and skin dryness. Carrots are know for there cancer fighting benefits and are an all over body tonic. 👍

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Nearly 15 months ago on August 26, 2013, I decided to see how long it would take me to fill up a Spaghettios can with test strips. Since then I have pricked my fingers approximately 2,010 times. In the 4 years and 11 months I’ve had type 1 diabetes, I have pricked my fingers an estimated 8,068 times. Not counting finger pricks, I have pierced my skin with a needle around 1,600 times. But it’s not just me. There are as many as 3 million Americans with type 1 diabetes. 80 people get diagnosed each day. We must do these things to stay alive. Type 1 diabetes is not “Diabeetus.” We didn’t ask for this, just like we didn’t do anything to cause it. It’s an autoimmune disease in which the insulin-producing beta cells are killed off. That means we have to take artificial insulin to stay alive, whether that be through shots or an insulin pump. There is NO CURE. Type 1 diabetics can’t “just exercise and eat right” to get rid of this disease. It is an everyday struggle for us to maintain a healthy blood sugar level. Some days we cry in defeat. Other days we smile in triumph. To all my fellow diabuddies: you may have diabetes, but remember that it will NEVER have you.

Diabetes: Type 1 vs Type 2

TYPE 1

Total lack of insulin

  •  5 to 10% of people who have diabetes.
  • autoimmune disease - immune system attacks beta cells in pancreas that produce insulin
  • eventually eliminating insulin production from the body.
  • cells cannot absorb glucose to produce energy
  • symptoms usually start in childhood or young adulthood. 
  • episodes of low blood sugar level (hypoglycemia) are common
  • cannot be prevented  
  • treated with insulin injections or pump

TYPE 2

 Too little insulin or cannot use insulin effectively 

  •  can develop at any age but most commonly becomes apparent during adulthood. 
  • vast majority of diabetics
  • body develops insulin resistance 
  • body compensates by producing much more, but can’t always produce enough and eventually beta cells may be destroyed from overwork - resulting in deficiency 
  • may not have symptoms before diagnosis
  • there are no episodes of low blood sugar level, unless the person is taking insulin or certain diabetes medicines.
  • can be prevented or delayed with a healthy lifestyle 

Both types increase a person’s risk for complications. Diabetes is the leading cause of blindness and kidney failure.

  • excessive build up of blood glucose causes an increase in osmotic pressure 
  • the kidneys no longer able to absorb most of the glucose - due to extreme concentration
  • the body pulls fluid from the tissues to try to dilute the blood and counteract the high glucose 
  • dehydrated tissues signal the need to drink more, subsequent increase in urination 

(Image caption: Production of APPsα in the brain: The nerve cells that encounter viral gene shuttles produce the therapeutic APPsα protein (orange) along with a green fluorescent protein. Brain region: hippocampus, important for learning and memory. Credit: S. Weyer, IPMB)

Protein Repairs Nerve Cell Damage

In laboratory experiments on the basic mechanisms that cause Alzheimer’s dementia, an international research team led by Heidelberg neurobiologist Prof. Dr. Ulrike Müller and a team of French scientists have succeeded in largely “repairing” the nerve cell damage typical in this disease. The researchers took a closer look at a key protein in Alzheimer’s pathogenesis, APP, and one of its cleavage products APPsα. Prof. Müller of Heidelberg University’s Institute of Pharmacy and Molecular Biotechnology explains that viral gene shuttles were used to drive the delivery of APPsα into the brains of Alzheimer´s mouse models. The protein APPsα in turn elicited repair effects and clearly improved memory. The researchers hope to use these findings to explore new approaches in the development of gene therapy for Alzheimer’s. Their results were published in the journal “Acta Neuropathologica”.

Alzheimer’s is the most frequent cause of dementia in the elderly. It particularly affects regions of the brain that are fundamental for memory and learning. The junctions through which the nerve cells communicate, the synapses, disappear long before the nerve cells die, damage that impairs both learning and memory. “While dead nerve cells are irretrievably lost, damaged synapses can be regenerated in the elderly,” Prof. Müller emphasises.

The brains of Alzheimer’s patients show plaque deposits, she explains. The deposits thwart the communication between the nerve cells and cause them to eventually die. The main component of the plaque is a short protein fragment known as the beta amyloid peptide. It is generated when the considerably larger amyloid precursor protein, or APP, is cleaved. “Until now, scientists believed that the overproduction of beta amyloid peptides was the main cause of Alzheimer’s. More recent investigations, however, have demonstrated that another APP cleavage product, the APPsα protein, also diminishes over the course of the disease,” Ulrike Müller continues. The protein cleaving enzymes, called secretases, play a key role in this process. The scissor-like secretases cut the APP cell surface protein at various positions. “These cleaving processes produce beta amyloid peptides that are toxic to the nerve cells, but also produce the protective APPsα cleavage product, which counteracts the toxic peptide,” says Prof. Müller. “Research over the last few years indicates that a misregulation of the secretase cleavage in Alzheimer’s results in inadequate production of protective APPsα.”

Earlier studies by Müller’s research group had already shown that APPsα has an essential function in the nervous system, particularly because it regulates the formation and function of synaptic junctions and spatial memory. These findings were used to investigate a new approach for a possible gene therapy for Alzheimer’s. The international research team used viral gene shuttles to introduce APPsα into the brains of mouse models with plaque deposits like those in Alzheimer’s. “After introducing the APPsα, we saw that the nerve cell damage could be repaired. The number of synaptic junctions increased, and spatial memory began to function again,” reports Ulrike Müller. “Our research results show the therapeutic effectiveness of APPsα in the animal model and open up new perspectives for the treatment of Alzheimer’s.”