A Yale University-led research team has developed a way to measure the loss of insulin-producing islet cells in the human pancreas. The death of those beta cells leads to diabetes. The finding is a crucial step in developing therapies to preserve insulin production and slow or halt the progress of diabetes.
Until now there has been no effective method for imaging pancreatic islet beta-cell mass in a non-invasive manner. Based on the work of Paul Harris and colleagues at Columbia University, the Yale team focused on the genetically expressed protein known as vesicular monoamine transporter type 2 (VMAT2). This protein facilitates the storage and release of some neurotransmitters, and is expressed simultaneously with insulin in pancreatic beta cells.
The Yale team infused both healthy patients and those with type-1 diabetes with a radioactive tracer that targets VMAT2. Patients were then scanned with a PET camera to calculate the radioactivity concentration in the pancreatic cells and measure the binding of the tracer.
Adjusting for dosage and body weight, the radiotracer binding among pancreatic cells was 40 percent less in type-1 diabetes patients than in healthy patients.
Senior author Gary W. Cline, associate professor of endocrinology at Yale School of Medicine, explained, ‘This tells us that we can now measure the loss of the pancreatic islet cells that produce insulin in diabetic patients. Being able to make these measurements will help in the development of a drug that can stop or slow the death of these cells, and thus prevent the damaging effects of type 1 diabetes.’ Yale University

A new JDRF-funded study shows that many of the genes known to play a role in type 1 diabetes (T1D) are expressed in pancreatic beta cells, suggesting that the cell responsible for producing insulin may be playing a part in its own destruction to lead to T1D. Researchers in Belgium suggest this interpretation after producing an extensive catalogue of more than 15,000 genes expressed in human islets, forming the most extensive characterisation of human islets reported to date.
The researchers, led by Decio Eizirik, M.D., Ph.D., professor and director of the Laboratory of Experimental Medicine at Universite Libre de Bruxelles in Brussels, Belgium, used a technique called RNA sequencing—a method that identifies all forms of transcribed RNAs in a cell—to assemble a catalogue that showed that more than 15,000 genes are expressed in healthy human islets. Transcribed RNA (ribonucleic acid) molecules serve as the vehicles through which a cell’s genetic information is expressed. The data has been made available to other researchers to be used for future studies of beta cell function.
In the study, the researchers found many of the previously known genes associated with T1D among the genes expressed in human islets. When the researchers exposed the human islets to agents (cytokines) released by immune cells that may trigger T1D, they noted changes in the expression patterns of these genes. This finding suggested that the islets may be contributing to the recruitment of immune cells as T1D starts to develop.
While conventional wisdom was that these genes played a role in T1D by affecting the function of the immune system, their expression in human islets led the scientists to consider the possibility that the beta cells—once seen as merely victims in T1D—might actually assist in their own attack by the immune system.
‘Based on our research, our understanding now is that type 1 diabetes in its early stages, is characterised by a dialog between beta cells and the immune system, instead of the previous view of beta cells as purely passive victims of the immune attack,’ said Dr. Eizirik. ‘We can now open our eyes a bit wider to the possible ways that type 1 diabetes can develop. As we expand our focus on beta cells, we could start to unearth more answers in the mystery of this disease.’
‘What we’re seeing is that beta cells may in fact be playing a larger role in triggering type 1 diabetes than we previously thought, and exploring this concept more deeply could lead to a better understanding of the what causes the autoimmune attack,’ said Julia Greenstein, Ph.D., JDRF’s assistant vice president for cure therapies. ‘Dr. Eizirik’s work is important to JDRF because it shows us that there is a need for more research on beta cell survival and health and its role as a potentially key part of the early disease process. Furthermore, the catalog of genes from this study will continue to support progress in many more areas of diabetes research.’ EurekAlert

The uproar that began last year when the U.S. Preventive Services Task Force stated that doctors should no longer offer regular prostate-cancer tests to healthy men continued this week when the task force released their final report. Overall, they stuck to their guns, stating that a blood test commonly used to screen for prostate cancer, the PSA test, causes more harm than good — it leads men to receive unnecessary, and sometimes even dangerous, treatments.
But many people simply don’t believe that the test is ineffective. Even faced with overwhelming evidence, such as a ten-year study of around 250,000 men that showed the test didn’t save lives, many activists and medical professionals are clamouring for men to continue receiving their annual PSA test. Why the disconnect?
In an article, researchers Hal R. Arkes, of Ohio State University, and Wolfgang Gaismaier, from the Max Planck Institute for Human Development in Berlin, Germany, picked apart lay-people’s reactions to the report, and examined the reasons why people are so reluctant to give up the PSA test.
‘Many folks who had a PSA test and think that it saved their life are infuriated that the Task Force seems to be so negative about the test,’ said Arkes.
They suggest several factors that may have contributed to the public’s condemnation of the report. Many studies have shown that anecdotes have power over a person’s perceptions of medical treatments. For example, a person can be shown statistics that Treatment A works less frequently than Treatment B, but if they read anecdotes (such as comments on a website) by other patients who had success with Treatment B, they’ll be more likely to pick Treatment B. The source of the anecdotes matters too. If a friend, a close relative, or any trusted source received successful treatment, they would be more likely to recommend that treatment to others, even if there was evidence showing the treatment only works for a minority of people.
Arkes and Gaismaier also propose that the public may have recoiled against the task force’s recommendations so fiercely because they weren’t able to properly evaluate the data in the report. Confusion over the use of control groups may have led people in the general public to weigh the data differently than medical professionals did.
‘How to change this is the million-dollar question,’ said Arkes. ‘Pictorial displays are far easier to comprehend than statistics. The two figures in our article depict the situation more clearly than text and numbers can do. I think data displayed in this manner can help change people’s view of the PSA test because we compare the relative outcomes of being tested and not being tested. Without that comparison, it is tough for the public to appreciate the relative pluses and minuses of the PSA test versus not having the PSA test.’
Men will be able to continue to request the PSA test, and it will be covered by health insurance for the foreseeable future. But psychological science suggests that unless people are convinced to choose statistics over anecdotes, confusion surrounding the test’s effectiveness will linger. Association for Psychological Science

In recent years it became clear that people with diabetes face an ominous prospect – a far greater risk of developing Alzheimer’s disease. Now researchers at The City College of New York (CCNY) have shed light on one reason why. Biology Professor Chris Li and her colleagues have discovered that a single gene forms a common link between the two diseases.
They found that the gene, known to be present in many Alzheimer’s disease cases, affects the insulin pathway. Disruption of this pathway is a hallmark of diabetes. The finding could point to a therapeutic target for both diseases.
‘People with type 2 diabetes have an increased risk of dementia. The insulin pathways are involved in many metabolic processes, including helping to keep the nervous system healthy,’ said Professor Li, explaining why the link is not far-fetched.
Although the cause of Alzheimer’s is still unclear, one criterion for diagnosis of the disease after death is the presence of sticky plaques of amyloid protein in decimated portions of patients’ brains.
Mutations in the human ‘amyloid precursor protein’ (APP) gene, or in genes that process APP, show up in cases of Alzheimer’s that run in families. In the study, Professor Li and her colleagues scrutinised a protein called APL-1, made by a gene in the worm Caenorhabditis elegans (C. elegans ) that happens to be a perfect stand-in for the human Alzheimer’s disease gene.
‘What we found was that mutations in the worm-equivalent of the APP gene slowed their development, which suggested that some metabolic pathway was disrupted,’ said Professor Li. ‘We began to examine how the worm-equivalent of APP modulated different metabolic pathways and found that the APP equivalent inhibited the insulin pathway.’
This suggested that the human version of the gene likely plays a role in both Alzheimer’s disease and diabetes.
They also found that additional mutations in the insulin pathway reversed the defects of the APP mutation. This helped explain how these genes are functionally linked.
The APL-1 is so important, they found, that ‘when you knock out the worm-equivalent of APP, the animals die,’ Li explained. ‘This tells us that the APP family of proteins is essential in worms, as they are essential in mammals,’ like us.
Professor Li and her colleagues hope that this new insight will help focus research in ways that might lead to new therapies in the treatment of both Alzheimer’s disease and diabetes. The City College of New York.

An international team of researchers have developed a new method for measurement of aggregated beta-amyloid – a protein complex believed to cause major nerve cell damage and dysfunction in Alzheimer’s disease. The new method might facilitate diagnosis and detection as well as development of drugs directed against aggregated beta-amyloid.
Alzheimer’s disease (AD) is the most common cause of memory decline and dementia. According to the Alzheimer World Report 2011, today around 36 million people suffer from Dementia (around 20 – 25 million are Alzheimer’s patients). These numbers will dramatically increase with the ageing populations over the next few decades. For the year 2050 the expected number of dementia patients will be 115 – 200 million (70 – 150 million Alzheimer’s cases). It is therefore important to develop new therapies and diagnostic methods to detect and treat this complex chronic neurodegenerative brain disease.
Alzheimer’s disease is characterised by aggregates in the brain, containing a protein called beta-amyloid. The neuropathology of Alzheimer’s disease has recently been linked to the neurotoxic amyloid-β (Aβ) oligomers. The crucial role of Aβ oligomers in the early events of AD is experimentally underlined. Several recent results suggest that those oligomers may cause the death of neurons and neurological dysfunctions relevant to memory. Furthermore Aβ oligomers levels are increased in brain and cerebrospinal fluid samples from people with Alzheimer’s disease. This reflects the potential of Aβ oligomers as a marker for the early diagnosis of the disease.
An international team of scien
He analysed the cerebrospinal fluid of 30 neurological patients, including 14 Alzheimer’s patients. ‘These samples provided from leading expert academic memory clinics in Germany and Sweden are of the best quality and are highly characterised in order to provide robust and reliable results on promising novel biomarker candidates’, Professor Harald Hampel of Frankfurt University, a lead investigator comments.
‘Because of the limited number of samples, however, further study is needed to confirm the results,’ said Dr. Oskar Hansson of Lund University. The study was an international co-operation with the University of California in the U.S., the Goteborg and Malmö Universities from Sweden and the University of Frankfurt in Germany.
The test might not only be used fo
tists from Germany, Sweden and the U.S. have used a new method to quantify soluble variants of aggregated beta-amyloid (Aβ oligomers) in cerebrospinal fluid by flow cytometry. "We found that patients with a greater number of Aβ oligomers in the cerebrospinal fluid had a more pronounced disease," says Dr. Alexander Navarrete Santos (the developer of this method and now employee of the Research Laboratory of the University of Halle, Department of Cardiothoracic Surgery), and first author of the study.r the early detection of AD but can also be used when developing new and effective therapies for AD. A decline in the number of Aβ oligomers in cerebrospinal fluids could be a hint for the effectiveness of new drug therapies. EurekAlert