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Copyright: © Richard Jacobs
This podcast comes at type 2 diabetes from all angles, and Venkate Narayan hopes global health policy will do the same. He and Richard discuss a newer understanding of the nuances of type 2 diabetes causes as well as the need to address it in low and middle-income countries. Listen and learn
K. M. Venkat Narayan is a professor in epidemiology at Emory University and director of the Emory Global Diabetes Research Center. Before Emory, he worked at the NIH and CDC. The center focuses on understanding the epidemiology of diabetes and its care for those diagnosed on a global scale. He emphasizes that type 2 diabetes is a global pandemic, affecting 435 million people world-wide, particularly in low to middle-income countries. While he says that type 2 diabetes was explained until recently as simply a disease of insulin resistance stemming from obesity and low activity, a newer understanding has emerged: type 2 diabetes symptoms really have multiple diseases under their umbrella, with different primary causes such as low insulin secretion.
In fact, researchers assert that there are at least five different types of type 2 diabetes and he explains some interesting studies along these lines. Most notably, they've shifted to emphasizing the role of poor insulin secretion and deposition of fat in specific places like the liver and how diet and physical activity affect that process. This research is exciting news for type 2 diabetics as this work makes precision medicine more likely for these patients. Dr. Narayan also addresses policy change. He says that while 90% of diabetes cases occur in low to middle-income countries, only 3 to 4% of research is happening in these countries. Because there are excellent treatments available for diabetics, he feels strongly that these treatments must be made available on a global scale. He describes how such global policy might be implemented to bring better diagnosis rates and treatment to these patients and curb the global effects of type 2 diabetes on health.
For more, see the Emory Global Diabetes Research Center site and find Dr. Narayan's work on PubMed. Available on Apple Podcasts: apple.co/2Os0myK
This podcast zeros in on an exciting therapy to address nerve damage caused by either trauma or disease. Paul Brennan, NervGen Pharma's CEO, tells how researchers identified this compound as a potential game changer by inhibiting factors contributing to nerve damage. Listen and learn
Paul Brennan is the president, CEO, and director of NervGen Pharma, a biotech company focused on therapies for patients who suffer from different nerve injury classifications. Their research on these different types, whether from trauma or neurodegenerative disorders, pointed out a common factor: scar tissue, which prevents nerve repair. There are chemicals in scar tissue called CSPGs, or chondroitin sulfate proteoglycans, and these chemicals are the focus of NervGen's new compound. Dr. Jerry Silver at Case Western discovered how CSPGs inhibit nerve growth through an interacting receptor that impedes the neuronal response. He was able to synthesize a peptide that works by "inhibiting the inhibition," and allowed growth, remyelination, and increased plasticity.
Paul Brennan explains how this works in clear and interesting terms, helping listeners understand facts about neurodegenerative diseases and nerve trauma along the way. Basically, CSPGs get "tuned up" in the body as a response to trauma and disease. They decrease inflammation and provide a structural element for protection. NervGen is designing their therapy to first let the CSPGs do what needs to be done and then have doctors utilize the compound, which is a synthesized peptide that disrupts and diminishes the receptor activity. He adds that this compound has the potential to address everything from Alzheimer's therapy to spinal cord injury treatment.
To follow the progress of their work, see their website: nervgen.com. Available on Apple Podcasts: apple.co/2Os0myK
This podcast explores an exciting discovery with implications for all neurodegenerative diseases and it centers on inflammation prevention. While inflammation is a known player in autoimmune diseases, researchers like Seth Masters have identified an inflammatory element in amyotrophic lateral sclerosis (ALS). Listen and learn
Seth Masters is an associate professor with the Walter and Eliza Hall Institute of Medical Research in Melbourne. His lab work centered on auto inflammatory syndromes and diseases from the context of autoimmunity—when the body is fighting against itself. Then, as with many significant moments in science, they took a step back and looked at the larger picture: they examined all the knowledge they'd acquired and asked if there were any other diseases in which this might play a role. Neurodegenerative diseases of the brain stood front and center as a strong possibility.
ALS is a particular form of neurodegenerative disease that's struck well-known figures like Stephen Hawking. These patients' muscles are not working because of damage impeding motor neuron function. Dr. Masters' group found that these motor neurons are sensitive to inflammation and caused them to die. Therefore, if doctors can prevent or slow down this inflammation, it will have a significant effect in slowing down the disease progression. He says that they are in safety phase 1 trials for drugs that will block that inflammation. He explains methodology for testing these drugs as well as an interesting description of how they hope to eventually identify the inflammation trigger. He tells listeners that may suffer from these diseases that there is "great hope" in what they've discovered and will make significant therapeutic strides. Listen in for more of this exciting news!
For more about his work, see his page on the institute's website: wehi.edu.au/people/seth-master Available on Apple Podcasts: apple.co/2Os0myK
This podcast offers a close up of the beginnings of type 1 diabetes and how one researcher is identifying pathways toward prevention. Type 1 diabetes, also known as insulin-dependent or juvenile onset diabetes, is not associated with causes like obesity as is type 2; rather, it's considered an autoimmune disease. Listen and learn
Ivan C. Gerling is a professor of medicine in endocrinology at The University of Tennessee Health Science Center. He explains that scientists have little understanding for why the immune system attacks the pancreas's beta cells, and thereby insulin production, which is the cause of type 1 diabetes. Because there's no safe way to biopsy a pancreas for living-tissue studies, it's been very difficult to get a close look at the mechanisms causing autoimmune diabetes symptoms. Furthermore, because there's no way for beta cell regeneration to naturally occur, preventing their destruction is key to preventing type 1 diabetes. However, a new organ-donation program has made a difference in allowing scientist like Dr. Gerling to study the pancreas tissue of type 1 diabetics.
His lab is researching whether certain viruses stress beta cells' function and trigger their eventual destruction. By comparing the beta cells and islets of Langerhans in type 1 diabetics with those who didn't suffer from the disease, they are finding some answers. Though they still have more work to do, they have found indications of stress and footprints of viral infections in the type 1 tissues. He adds that they're identifying the stress pathways that seem to be activated when these beta cells start going downhill. This will help them identify drugs to help the stressed cells, and, if it turns that the first causes are the viral infections, they hope to identify these viruses specifically and create vaccines for them. Listen in to learn more about these steps forward in medical research. Available on Apple Podcasts: apple.co/2Os0myK
Nearly one hundred years ago, the lives of people with type I diabetes were forever changed, for the better: insulin was discovered. Since then, people with type I diabetes have been treated with insulin, and the disease itself has been regarded as a manifestation of an autoimmune response. But is the immune system the only thing that triggers type I diabetes, or is there something else which signals the immune response? Press play to learn:
Dr. Raghu Mirmira is Professor of Medicine in the Section of Endocrinology, Diabetes & Metabolism at the University of Chicago, where his research revolves primarily around the signals that cause the immune response which leads to type I diabetes. Contrary to the predominant belief for over 90 years, Dr. Mirmira and his colleagues are learning that pancreatic beta cells send a signal which activates the immune system to respond in a way that ultimately causes the manifestation of type I diabetes. This understanding shifts the focus from being solely on the immune system, to being in large part on these beta cells.
According to Dr. Mirmira, preventing this disease is about figuring out how beta cells turn on these signals, and how to prevent them from doing so. A complicating factor in this type of research is the inability to harvest human beta cells. Instead, two methods of studying the cell are being utilized: one that harvests these cells from mice and fish, and one that involves induced human pluripotent stem cell-derived beta cells.
From research with mice and fish beta cells, Dr. Mirmira and his team have learned that there is a stress cascade in the beta cell. Essentially, this cascade is triggered when something in the environment sends a negative signal to the beta cell, causing the beta cell to produce emergency proteins in the cell. So many proteins are produced that they become disorganized and misfolded, and have nowhere to go; as a result, some leave the beta cell and end up on its surface, exposed to the body's immune system. Recognizing these misfolded proteins as foreign, the immune system attacks them, killing the beta cells to which they are attached. When enough beta cells have been destroyed, the symptoms of type I diabetes manifest.
Dr. Mirmira discusses the ins and outs of all this and more, including the pathophysiology of diabetes type I in general, the role and function of islet cells in diabetes, an ongoing national birth cohort study on type I diabetes, how the microbiome may (or may not) be connected to type I diabetes, what it means to say there are endotypes of people who have diabetes, antigen spreading, misfolded insulin and what this triggers in the body, and where Dr. Mirmira hopes his research will lead.
For access to Dr. Mirmira's original research, search his name on PubMed or Google Scholar. Stay up to date on the latest by visiting https://voices.uchicago.edu/mirmiralab/. Available on Apple Podcasts: apple.co/2Os0myK
Over the past 60 years, the incidence of type I diabetes in parts of the word has increased sixfold, and we don't know why. In the Eizirik Lab at the Indiana Biosciences Research Institute, Dr. Decio Eizirik and his team research type 1 diabetes in a way that not many others do. Press play to discover:
Type I diabetes is an autoimmune disease wherein the immune system begins recognizing pancreatic beta cells as foreign, and attacks and destroys them as a result. As the disease progresses, the type 1 diabetes patient will lose most of their pancreatic beta cells, which are responsible for the production of insulin. Consequently, these patients become dependent upon insulin for the rest of their lives, often requiring continuous glucose monitoring and multiple insulin injections per day.
Most research on this disease has focused primarily on the immune system, but in the Eizirik Lab, the focus is more on the pancreatic beta cells, and the dialogue between these cells and the body's immune system. It is Dr. Eizirik's goal to qualify the words that comprise this dialogue, to understand why and when it goes wrong, and to determine whether there's a way to make this dialogue more 'polite.'
Dr. Eizirik discusses the details of his research and more, including the specific functions of beta cells, therapies that target the T cells of the immune system, attempts at combining therapies and reeducating the immune system, the role of extracellular vesicles, chemokines, and cytokines in the dialogue between beta cells and the immune system, and the possibility of natural beta cell regeneration.
https://www.indianabiosciences.org/eizirik/research Available on Apple Podcasts: apple.co/2Os0myK
An implantable bioartificial kidney system that does what dialysis can't do; this is what's being developed as part of The Kidney Project at University of California, San Francisco and Vanderbilt University. Press play to learn:
Lynda Frassetto is Professor Emeritus of Medicine in the Division of Nephrology at the University of California, San Francisco. She spends some of her time taking care of nephrology patients, and some of her time working with William Fissell, MD and Shuvo Roy, PhD, who lead The Kidney Project. Dialysis can keep patients alive by filtering toxins out of the blood, which is what healthy kidneys do. But what happens to the fluid after it's been filtered?
In healthy bodies, the fluid goes through kidney tubules, where it responds to chemical signals which might dictate that more water or salt be resorbed, and/or that more creatinine, phosphorus, urea, or other acids be removed. After the toxins have been filtered, the fluid is subjected to the feedback systems of the body, which is essential to keeping the body's water and chemical levels where they should be. This is something that dialysis simply cannot accomplish, but it's not too great a task for the artificial system being created; this system has renal tubular cells, so it can keep the body's water and chemistry levels in check, which translates to better quality of life for patients.
Press play for the details of all this and more, including where in the body it is placed, how it stacks up against transplanted kidneys in terms of normal kidney function, when it might receive FDA approval for testing in humans, and what the first clinical trials will look like.
Visit https://pharm.ucsf.edu/kidney to learn more. Available on Apple Podcasts: apple.co/2Os0myK
Not all body fat is the same. Scientists have identified the presence and significance of brown fat in adult humans. Shing Kajimura researches brown fat and how its presence curbs obesity and type 2 diabetes as well as other metabolic diseases. Listen and learn
Shingo Kajimura is with Harvard Medical School's Beth Israel Deaconess Medical Center and works in the endocrinology, diabetes, and metabolism division. He's interested in molecular bases by which we adapt to different environmental stresses like nutritional changes, dietary changes, and even temperature changes. Enter brown fat. Adult humans have brown fat around their neck, almost like an internal scarf, and in a few other areas. When we got cold and shivering can no longer do the trick to warm us, brown fat's thermogenesis steps in. He explains exactly how it undergoes a molecular process similar to how a light bulb emits energy, which in turns eats up glucose and lipids. Enter type 2 diabetes causes.
This brown fat activity has associations with improved lipid and glucose handling. Because it eats up glucose and lipids, it is a significant "metabolic sink" for these molecules. It literally takes up glucose and combusts it in cells. Unfortunately, we can't just deposit brown fat in people as a type 2 diabetes cure. He explains how climate, which also implicates seasonality, and age connect to brown fat presence. There's a significant decrease in brown fat when we hit our forties and fifties. Cold adaptation is also a factor, and the body starts making brown fat fairly quickly after cold exposure. All these factors make the issue a little more complicated and Dr. Kajimura explains how in very clear terms. There is hope that this research may benefit those of us that could benefit from more brown fat. He comments that researchers are looking at bio medics to make our fat cells feel cold without our brain actually thinking the same.
For more about his work, see his lab's web page: kajimuralab.org. Available on Apple Podcasts: apple.co/2Os0myK
Working on COVID-19? This podcast is for you. This episode offers a valuable conversation with a comprehensive yet detailed understanding of SARS CoV-2 pathogenicity. Listen in as a front-line researcher discusses the computational biology of COVID-19 from three directions: the viral action, the human response, and environmental influences on both. Listen and hear
Daniel A. Jacobson is a computational systems biologist at Oak Ridge National Laboratory. Oak Ridge is part of the national laboratory system in the U.S., and has access to world-wide data and top researchers. His lab is tracking all the SARS CoV-2 sequence data from around the world and finding significant patterns that may impact pathogenicity and looking at evolutionary patterns that may give insights. He shares an invaluable level and type of information with listeners in this conversation, explaining exactly how COVID-19 infects cells and what pathways it disrupts. For example, he explains how after looking at the "dynamic tension" points in normal systemic pathways, they were able to identify how this virus disrupts specific aspects of the RAS pathway, kallikrein system, and vitamin D reception in infected patients. The resulting bradykinin storm and increased hyaluronic acid leads to the symptoms doctors find so difficult to overcome such as hydrogel in the lungs.
But there's good news too: they've identified a number of pharmaceuticals that can help in these metabolic pathways, even down to vitamin D regulation. Currently, researchers have identified three different drugs that do what the lab's mechanistic models predicted and help patients suffering from the virus. He adds that they are expanding their list, hoping to identify a larger battery of drugs that will also help. He says there's a significant push to join forces with clinical colleagues and explore multiple common therapies. He also discusses the mutation patterns. They are identifying how the virus changes over the course of the pandemic and trying to infer how those changes will impact pathogenicity. Then they can observe how those changes are promulgating in the human population. Finally, they are also plugging in environmental components.
Find their papers in eLife, Molecular Biology and Evolution, and bioRxiv and google them for more. Available on Apple Podcasts: apple.co/2Os0myK
Exercise: will it make your blood sugar go high, or low…and what can be done about it? The answer depends on a number of factors. For over 25 years, Michael C. Riddell has focused his research on the area where kinesiology and diabetes meet. Press play to learn:
Riddell is Full Professor in the School of Kinesiology and Health Science at York University, where his research program is aimed at examining the mechanisms that underlie exercise in people with pre-diabetes or type I or type II diabetes. Why is exercise beneficial, and what are the challenges that come along with it in terms of fluctuating blood glucose levels? What type of technology can be employed to decrease the chances of glucose levels dipping too low or shooting too high during exercise? These questions are being explored by Riddell and his team, and he discusses the details of what they've discovered so far.
He also discusses the impressive amount of valuable information hat has been gained from continuous glucose monitoring (CGM), why doctors and scientists are pushing for ambulatory glucose profiles using CGM as opposed to A1C tests, in what way the addition of glucagon to insulin pumps can act as the "brakes" when blood sugar levels get too high, and more.
For access to Riddell's lectures and papers on these topics and more, visit https://mriddell.lab.yorku.ca/. Available on Apple Podcasts: apple.co/2Os0myK
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