Researchers from the Australian National University have identified heparan sulfate (HS) as being essential for beta cell survival. Whilst this compound is known to be involved in a number of other biological activities, this is the first time it has been implicated in the development of type 1 diabetes.

The study suggests that levels of HS in insulin-producing beta cells are depleted as a result of the autoimmune attack that causes type 1 diabetes. When levels are reduced, the cells are defenceless against damage from common byproducts of metabolism and die. The study went on to demonstrate that replacing HS, or treating the beta cells to preserve HS levels, protected against development of type 1 diabetes.

These findings have not only identified HS as a potential new therapeutic target for the prevention of type 1 diabetes onset, it has also opened up the possibility of HS levels being used as a marker of disease onset and as a method of protecting islet cells that have been isolated and transplanted.

Whilst the initial research was conducted in mice, JDRF has provided further funding to provide proof of concept in humans.

J Clin Invest. 2012;122(1):132–141. doi:10.1172/JCI46177.

Some of the interesting insights gained include:

• Identifying the specific blood vessels where the T cells enter the pancreas
• How the T cells launch a random attack on the beta cells
• How long it actually takes to kill beta cells

These insights have already started to explain some mysteries about type 1 diabetes, and opens potential new research avenues.

The video was made possible through the use of a two-photon microscope that allows researcher to “see” into living tissue, and the development of a procedure that allowed the microscope to be used in the pancreas, which had always been too small, soft, and difficult to access.

Head of Research Development at JDRF Australia, Dr Dorota Pawlak PhD says “This dynamic view will provide the worldwide scientific community with incredible insights into this disease process. These videos can affect future directions in type 1 diabetes research.”

J Clin Invest. December 2011, DOI:10.1172/JCI59285

The Awards recognise two outstanding researchers in type 1 diabetes with the publication or patent demonstrating the highest innovation, impact and importance in the 2010 calendar year.

Winner – Established Researcher – Dr David O’Neal
Winner – Early Career Researcher – Helen Thomas PhD

JDRF CEO Mike Wilson congratulated to the two researchers. “The term innovation is used often, but it is the holy grail of medical research. The JDRF Macquarie Group Foundation Diabetes Research Innovation Awards awards are significant because they recognise impact as well as innovation.”

“The work of these researchers is not just new, it has demonstrable potential to change the lives of people with type 1 diabetes.”

Dr David O’Neal is Senior Lecturer, Department of Medicine at the University of Melbourne. His work helps to empower people with type 1 diabetes who are using the latest diabetes management technology to make the best decisions with the information produced by continuous glucose monitors.

“We wanted to deliver an educational algorithm that would be a tool to help people to respond in the best way to glucose information – both immediately and retrospectively.”

Helen Thomas PhD is a NHMRC Career Development Fellow at St Vincent’s Institute in Melbourne. Her work was a breakthrough in the understanding of how insulin producing cells – known as beta cells – live and die. The goal is finding ways to protect these cells, primarily for people who have just been diagnosed with type 1 diabetes, as well as those who have received transplants of insulin producing cells.

“Understanding how beta cells are killed in type 1 diabetes is very important if we are to stop the immune system response that leads to their death. Importantly, the molecules identified in this work have unique structure and function making the design of drugs for their inhibition possible.”

The winners of each Award receive a personal award and a cash prize of $5,000 to be used for the advancement of their research career in the field of type 1 diabetes.

The Diabetes Innovation Awards are supported by the Macquarie Group Foundation through its pioneering, long term partnership with the Juvenile Diabetes Research Foundation.

It has been known for some time that glucose is a key factor in the growth of beta cells. However, it’s not as simple as increasing blood glucose to re-grow beta cells, because inducing high levels of glucose in the blood has serious health implications that can include blindness, stroke and kidney failure.

Lead researcher Yuval Dor PhD, from the Hebrew University of Jerusalem, used a combination of techniques to encourage beta cells to reproduce themselves, including the manipulation of an enzyme known as glucokinase, which senses blood glucose and tells cells how to respond.

The surprise was the beta cells response: they increased their rate of regeneration in response to the message from the enzyme glucokinase, not the actual blood glucose levels themselves.

This finding gives hope to the type 1 diabetes community because drugs that activate glucokinase are currently being developed for those with type 2 diabetes, to increase their production of insulin.

“Our work shows that as glucose is metabolised, it tells the beta cells to regenerate. It is not blood glucose per se that is the signal, but the glucose-sensing capacity of the beta cell that’s the key to regeneration,” says Dor, who is also the 2010 recipient of a JDRF Research Award.

“Beta cells, contrary to expectations, do have a regenerative capacity. It’s slow, it’s weak. It may be defective in diabetics, but it’s there,” said Dor.

JDRF Australia’s Head of Research Development, Dr Dorota Pawlak PhD, says beta cell regeneration is a key area of focus for curing type 1 diabetes.

“Beta cells are the victims of the autoimmune attack that causes type 1 diabetes. In combination with stopping that attack, re-growth or transplant of beta cells using techniques like this will be the key to restoring health and curing this disease.”

Cell Metabolism Vol 13 Issue 4, e-pub 6 April 2011: 440-449

The JDRF-funded researchers developed a ‘reagent’ or chemical agent that allowed mice with diabetes to accept donor cells from an islet transplantation as their own, with no need for immunosuppressive drugs.

The reagent works against a harmful molecule known as IL-21, which appears to be associated with type 1 diabetes. By combating the body’s own killer immune cells, the drug prevents the transplanted islet cells from being destroyed.

What is islet transplantation?

Islet transplantation involves the transplant of groups of insulin secreting cells (islet cells) from a deceased organ donor to a patient with type 1 diabetes. The transplantation of islet cells is much less invasive than a whole organ transplant because the cells are either infused through a catheter or inserted through a small incision in the abdomen.

Most islet transplant recipients require as standard at least two transplants. This means at least two deceased organ donors are needed for a ‘cure’. The procedure is followed by a regime of immunosuppression, because the body identifies the islet cells as foreign and will attack them.

The autoimmune process that killed the body’s own islet cells in the first place will also attack these cells without immunosuppression. For these reasons, islet transplantation is currently only available to adults with brittle diabetes or hypo-unawareness, where life with type 1 diabetes has become unmanageable. Read more about islet transplantation here.

Why is this research important?

Dr Cecile King from the Garvan said “Individual tissue types have their own molecular signature, and our bodies usually reject tissues they don’t recognise. In our experiments we used a very strong mismatch, and the mice still accepted the transplants without rejection.”

“If this works in people as it has in mice, then they would only have to take the drug for a brief time-window after surgery– then the transplant would be fine for life.”

“The next step would be to trial our IL-21 neutralising agent in people.”

Dr Dorota Pawlak, JDRF’s Head of Research Development, said that the ability to replace insulin producing cells safely in people with type 1 diabetes, without the need for immunosuppression, would be a revolution for diabetes research.

“This finding represents progress and it is important to acknowledge and honour advances that take us closer to finding a cure for type 1 diabetes.”


Read more about this research here or review the full paper here.

The partnership will support a three-year, $1.4 million pre-clinical research program at the University of Geneva, led by Dr. Pedro Herrera.

Why is it important?
Regeneration is a key component of the Beta Cell Therapies Pathway, which aims to restore the body’s ability to make its own insulin.

This collaboration could be “a critical opportunity to nurture new strategies to restore insulin production in people with type 1 diabetes,” said Patricia Kilian PhD, JDRFI’s Director of Regeneration Programs.

“The goal of this research agreement is to understand how selected cells can be reprogrammed in order to convert them into insulin-producing cells in the body,” said Lilly’s chief scientific officer for diabetes drug discovery, Philip Larsen PhD.

“This research is an example of regenerative medicine, a new frontier in science that replaces or regenerates new cells, tissues or organs, and while this particular research is early stage, it may ultimately lead to new approaches to treating type 1 diabetes.”

How does it work?
Restoring insulin production through regeneration involves triggering the body to grow its own new beta cells, either by growing existing ones – some are usually still active, even in people who have had diabetes for decades – or by creating new ones by reprogramming, which involves converting one type of cell in the body into a different type.

The ultimate goal for the regeneration of beta cells is to eliminate the need for insulin.

Read more about JDRF’s Research Strategy and Beta Cell Therapies
Read more about Eli Lilly and Diabetes
Find out more about type 1 diabetes

It’s been known for a while that women can produce new beta cells to allow for the increase in insulin needed to supply energy during pregnancy but how this happens has been a mystery. In an exciting new discovery, a team of JDRF researchers have identified key steps in this process and shown that serotonin is one of the triggers.

According to lead researcher Dr Michael German, from the University of California, pregnancy hormones turn on a gene in the pancreas, causing in the production of serotonin in the pancreas which acted to stimulate the production of new beta cells. Researchers also showed that the process can also be reversed to stop beta cell production.

While at first glance they may not seem to be a significant breakthrough for people with type 1 diabetes, it actually has tremendous implications for the development of new regeneration treatments.

“These findings uncover a previously unknown pathway with a relatively simple trigger,” says JDRF Head of Research Dr Dorota Pawlak, “and provided answers to some fundamental questions limiting our progress in the JDRF beta cell regeneration program.”

“The primary aim of this research area is to trigger the body to produce its own beta cells, either by copying existing ones or inducing the pancreas to make new ones. By doing this we can enable people with type 1 diabetes to produce their own insulin without the need for transplant surgery.”

“The next step for this research is to identify specific mechanisms along the pathway that could be used as a safe and effective target for new beta cell regeneration therapies.”

Type 1 diabetes is caused when a persons own immune system attacks and destroys the insulin-producing cells in the pancreas. Whilst the precise trigger of this attack is still unproven, researchers do know that there are certain immune cells that play a more important role than others. The challenge is to target the “bad” cells without harming the good cells that protect us from day-to-day infections.

Publishing their results this week in the international journal Immunity, JDRF-funded researchers from the University of Calgary have done just that. They have developed a vaccine that when tested in a mouse model of diabetes reduced the aggressive immune attack on beta cells by boosting the number of protector cells.

The first step of this program was to develop a way to safely increase protector cell numbers, and they did this using an exciting new scientific discipline known as nanotechnology. Nanotechnology involves the intricate manipulation of tiny particles that measure between 1-100 nanometres in size – equivalent to one billionth of a metre or 1/100,000 the width of a normal sheet of paper.

In this case, the researchers created a “nanovaccine” involving tiny spheres especially coated with a protein specific to type 1 diabetes. When introduced into the immune system of diabetic mice, these spheres triggered the production of good protector cells and reduced the number of bad aggressive cells.

The end result was that the nanovaccine prevented diabetes in a pre-diabetic mouse model and restored normal blood glucose levels in diabetic mice.

Whilst the lead researcher Dr Pere Santamaria says the results are not immediately transferable to humans, research is already underway into understanding what needs to be done to translate this knowledge into clinical trials.

The development of a safe and effective vaccine for type 1 diabetes is a top priority for JDRF internationally, and there are many other similar programs making progress in this area around the world.

Under healthy conditions, beta cells regenerate slowly to respond to increased insulin requirements or to replace those lost by injury. In the case of type 1 diabetes however, the beta cells are destroyed faster than they can naturally regenerate.

For the last decade, researchers around the world have been working towards developing ways to either re-grow remaining beta cells, or transplant new beta cells that have been genetically modified to be invisible to the immune system.

In this case, the research team led by Dr Pedro Herrera at the University of Geneva in Switzerland, took a slightly different approach. They killed off all functioning beta cells in a special population of mice then gave the mice insulin therapy whilst using fluorescent dyes to track what happened to the cells in their pancreas over the next year.

What they found is that another group of pancreas cells – the alpha cells – spontaneously reprogrammed themselves over time to take over the role of insulin production.

Alpha cells reside next to beta cells in the pancreatic and normally produce glucagon – a hormone that has the opposite effect of insulin. In this case, researchers found that after they were reprogrammed, they produced both glucagon and insulin in quantities sufficient enough to maintain normal blood glucose levels.

Dr Dorota Pawlak

Dr Dorota Pawlak, Head of Research Development for JDRF Australia says that this is an enormously exciting discovery for type 1 diabetes research.

“This research is the first to show that it is possible to spontaneously regenerate insulin-producing cells from other pancreatic tissue without having to resort to complex and potentially dangerous drug treatments.”

“The key difference between this study and others is all the beta cells were removed.”

“It is believed that a small number of beta cells still exist in the pancreas of people with type 1 diabetes, even after many years of living with the disease. This research showed simply removing all the beta cells in mice naturally triggered the re-programming process in the alpha cells.”

“Whilst it is important to remember that this research was conducted in mice and therefore is not immediately transferable to humans, it is a great step forward and will ultimately lead to the development of new therapies to reverse and cure type 1 diabetes.”

JDRF is a world leader in the field of beta cell regeneration. Find out more about beta cell regeneration.

These findings reinforce the potential of regeneration as a cure for diabetes and provide insights for discovering new approaches to treat people with diabetes by restoring or regenerating their ability to produce insulin.

JDRF- funded researchers at the Salk Institute for Biological Studies in California showed that the stress hormone CRF (corticotropin-releasing factor) could increase the rate at which insulin-producing cells in the pancreas expand in animal models. 

Dr Wylie Vale, Ph.D., Professor and Head of the Clayton Laboratories for Peptide Biology said that being able to stimulate beta cells to divide faster “may be part of a solution that may ultimately, hopefully, allow management of type 1 diabetes.”

“But because type 1 diabetes is an autoimmune condition, making the cells divide won’t be enough. That is why researchers are working hard to solve the problem of destruction of beta cells.”

See JDRF International for more information.