A new research result from Aarhus University and the Steno Diabetes Center Aarhus has identified how diabetes affects stem cells residing in muscle to form fat and connective tissue. According to the researchers, the discovery has major clinical perspectives.
The cells that researchers from Aarhus University and the Steno Diabetes Center Aarhus have found are located in the skeletal muscle, but also in a many other organs. They are responsible for creating fat and scar tissue. Unhealthy skeletal muscle with an accumulation of connective tissue (fibrosis) and fat cells (called adipogenesis in medicine) damage the muscle's function.
In this study, the researchers have studied how type 2 diabetes alters the skeletal muscles. They discovered that both fibrosis and fatty tissue are formed in the muscles.
"One characteristic of e.g. diabetes is that the tissue becomes filled with fat and scar tissue," says Jean Farup.
Huge potential
He therefore believes that the clinical perspective can be huge, because the cells are found all over the body, and because many diseases are associated with exactly this build-up of fat and scar tissue in the skeletal muscle and other organs.
"With the help of studies of gene expression at single cell level, we've simply found the fibrosis-forming and fat-accumulating cells in the skeletal muscle," he explains.
The researchers also uncovered how gene expression occurs in an unhealthy cell compared to a healthy cell. Once they had identified the cells, they examined how the cells changed in a person with type 2 diabetes.
A novel approach to treating type 2 diabetes is being developed at the Technion. The disease, caused by insulin resistance and reduction of cells' ability to absorb sugar, is characterised by increased blood sugar levels. Its long-term complications include heart disease, strokes, damage to the retina that can result in blindness, kidney failure, and poor blood flow in the limbs that may lead to amputations. It is currently treated by a combination of lifestyle changes, medication, and insulin injections, but ultimately is associated with a 10-year reduction in life expectancy.
Led by Professor Shulamit Levenberg, Ph.D. student Rita Beckerman from the Stem Cell and Tissue Engineering Laboratory in the Technion's Faculty of Biomedical Engineering presents a novel treatment approach, using an autograft of muscle cells engineered to take in sugar at increased rates. Mice treated in this manner displayed normal blood sugar levels for months after a single procedure. The group's findings were recently published in Science Advances.
Muscle cells are among the main targets of insulin, and they are supposed to absorb sugar from the blood. In their study, Prof. Levenberg's group isolated muscle cells from mice and engineered these cells to present more insulin-activated sugar transporters (GLUT4). These cells were then grown to form an engineered muscle tissue, and finally transported back into the abdomen of diabetic mice. The engineered cells not only proceeded to absorb sugar correctly, improving blood sugar levels, but also induced improved absorption in the mice's other muscle cells, by means of signals sent between them. After this one treatment, the mice remained cured of diabetes for four months—the entire period they remained under observation. Their blood sugar levels remained lower, and they had reduced levels of fatty liver normally displayed in type 2 diabetes.
An increasing number of studies suggest a link between a neighborhood's built environment and the likelihood that its residents will develop chronic diseases such as heart disease, type 2 diabetes (T2D) and certain types of cancers. A new nationwide study led by researchers from NYU Grossman School of Medicine published online today in JAMA Network Open suggests that living in neighborhoods with higher availability of fast-food outlets across all regions of the United States is associated with higher subsequent risk of developing type 2 diabetes.
Findings also indicated that the availability of more supermarkets could be protective against developing T2D, particularly in suburban and rural neighborhoods.
New research could form the basis for developing life-changing therapies that limit the impact of diabetic eye disease—a condition that could potentially affect some 1.7 million Australians, suffering from type 1 and type 2 diabetes.
Published in PNAS, University of Melbourne research uncovers how retinal immune cells change during diabetes, which may lead to new treatments that can be used from an early stage of disease, well before any loss of vision.
"Until recently, immune cells of the nervous system were thought to sit quietly, only responding when injury or disease occurred. Our finding expands our knowledge of what these cells do and shows a highly unusual mechanism by which blood vessels are regulated. This is the first time, immune cells have been implicated in controlling blood vessel and blood flow," co-author Professor Erica Fletcher said.
(EurekAlert) Intensive lifestyle intervention with plenty of exercise helps people with prediabetes improve their blood glucose levels over a period of years and thus delay or even prevent type 2 diabetes. In particular, individuals with prediabetes at highest risk benefited from intensive lifestyle intervention. This is shown by the evaluation of the Prediabetes Lifestyle Intervention Study (PLIS) of the German Center for Diabetes Research (DZD), which was conducted at 8 sites of the center throughout Germany. The results have now been published in the journal Diabetes.
More exercise and healthy eating behavior help many people with prediabetes to normalize their blood glucose levels and avoid developing type 2 diabetes. However, not everyone benefits from a conventional lifestyle intervention (LI). Recent studies show that already in prediabetes, there are different subtypes with different risk profiles. Researchers at the German Center for Diabetes Research (DZD) have therefore investigated in a multicenter randomized controlled trial whether people with prediabetes and a high risk benefit from an intensification of the intervention and how people with a low risk are affected by a conventional LI compared to no lifestyle changes.
The LI lasted 12 months in each case and the follow-up period was a further two years. A total of 1,105 individuals with prediabetes were investigated at various study sites in Germany and assigned to a high-risk or low-risk phenotype based on insulin secretion, insulin sensitivity, and liver fat content. 82% of participants completed the study.
(EurekAlert) Overweight or obesity, an unfavorable distribution of fat in the body and the development of type 2 diabetes are often associated with a reduced effect of the hormone insulin in many organs, including the brain (insulin resistance). So far there is no treatment to restore insulin sensitivity in the brain, which plays a key role in metabolic control. Researchers of the German Center for Diabetes Research (DZD), the departments of Internal Medicine IV (Director: Prof. Andreas Birkenfeld) and Clinical Chemistry and Pathobiochemistry (Director: Prof. Andreas Peter) of Tübingen University Hospital and the Institute of Diabetes Research and Metabolic Diseases (IDM) at Helmholtz Munich have now shown for the first time that the SGLT2 inhibitor empagliflozin can be used to treat insulin resistance in the brain – with positive effects on the metabolism of the entire body. This study has now been published in Diabetes Care.
The brain has a decisive influence on our eating behavior and thus also on body weight and metabolism. If the brain reacts sensitively to insulin, we eat less, less abdominal fat is stored, and the insulin sensitivity of the entire body improves. However, in people with obesity or type 2 diabetes, the hormone in the brain is no longer effective. This insulin resistance leads to a disturbed metabolism. So far, insulin resistance in the brain cannot be treated with drugs. The researchers investigated whether a diabetes drug from the SGLT2 inhibitor group can also reverse insulin resistance in the brain. SGLT2 inhibitors reduce elevated blood glucose levels in diabetes by promoting glucose excretion through the urine and have a beneficial effect on the heart, circulation and kidneys. For this purpose, the effect of the SGLT2 inhibitor empagliflozin on the insulin sensitivity of the brain was investigated in study participants with a preliminary stage of diabetes (prediabetes).
The discovery of insulin 100 years ago opened a door that would lead to life and hope for millions of people with diabetes. Ever since then, insulin, produced in the pancreas, has been considered the primary means of treating conditions characterized by high blood sugar (glucose), such as diabetes. Now, Salk scientists have discovered a second molecule, produced in fat tissue, that, like insulin, also potently and rapidly regulates blood glucose. Their finding could lead to the development of new therapies for treating diabetes, and also lays the foundation for promising new avenues in metabolism research.
The study, which was published in Cell Metabolism on January 4, 2022, shows that a hormone called FGF1 regulates blood glucose by inhibiting fat breakdown (lipolysis). Like insulin, FGF1 controls blood glucose by inhibiting lipolysis, but the two hormones do so in different ways. Importantly, this difference could enable FGF1 to be used to safely and successfully lower blood glucose in people who suffer from insulin resistance.
"Finding a second hormone that suppresses lipolysis and lowers glucose is a scientific breakthrough," says co-senior author and Professor Ronald Evans, holder of the March of Dimes Chair in Molecular and Developmental Biology. "We have identified a new player in regulating fat lipolysis that will help us understand how energy stores are managed in the body."
Individuals living with Type 1 diabetes must carefully follow prescribed insulin regimens every day, receiving injections of the hormone via syringe, insulin pump or some other device. And without viable long-term treatments, this course of treatment is a lifelong sentence.
Pancreatic islets control insulin production when blood sugar levels change, and in Type 1 diabetes, the body's immune system attacks and destroys such insulin-producing cells. Islet transplantation has emerged over the past few decades as a potential cure for Type 1 diabetes. With healthy transplanted islets, Type 1 diabetes patients may no longer need insulin injections, but transplantation efforts have faced setbacks as the immune system continues to eventually reject new islets. Current immunosuppressive drugs offer inadequate protection for transplanted cells and tissues and are plagued by undesirable side effects.
Now a team of researchers at Northwestern University has discovered a technique to help make immunomodulation more effective. The method uses nanocarriers to re-engineer the commonly used immunosuppressant rapamycin. Using these rapamycin-loaded nanocarriers, the researchers generated a new form of immunosuppression capable of targeting specific cells related to the transplant without suppressing wider immune responses.
The paper was published today, in the journal Nature Nanotechnology. The Northwestern team is led by Evan Scott, the Kay Davis Professor and an associate professor of biomedical engineering at Northwestern's McCormick School of Engineering and microbiology-immunology at Northwestern University Feinberg School of Medicine, and Guillermo Ameer, the Daniel Hale Williams Professor of Biomedical Engineering at McCormick and Surgery at Feinberg. Ameer also serves as the director of the Center for Advanced Regenerative Engineering (CARE).
An artificial pancreas developed by a team of Cambridge researchers is helping protect very young children with type 1 diabetes at a particularly vulnerable time of their lives. A study published today found that it is both safe to use and more effective at managing their blood sugar levels than current technology.
Writing in the New England Journal of Medicine, researchers compared the performance of the artificial pancreas, which uses an algorithm to determine the amount of insulin administered by a device worn by the child, against 'sensor-augmented pump therapy'.
Management of type 1 diabetes is challenging in very young children, because of a number of factors including the high variability in levels of insulin required and in how individual children respond to treatment, and their unpredictable eating and activity patterns. Children are particularly at risk of dangerously low blood sugar levels (hypoglycaemia) and high blood sugar levels (hyperglycaemia). Previous studies have linked prolonged hyperglycaemia in children with type 1 diabetes with lower IQ scores and slower brain growth.
To manage children's glucose levels, doctors increasingly turn to devices that continuously monitor glucose levels and deliver insulin via a pump, which administers insulin through a cannula inserted into the skin. These devices have proved successful to an extent in older children, but not in very young children.
Use of the drug verapamil to treat Type 1 diabetes continues to show benefits lasting at least two years, researchers report in the journal Nature Communications. Patients taking the oral blood pressure medication not only required less daily insulin two years after first diagnosis of the disease, but also showed evidence of surprising immunomodulatory benefits.
Continuing medication was necessary. In the two-year study, subjects who stopped daily doses of verapamil at one year saw their disease at two years worsen at rates similar to those of the control group of diabetes patients who did not use verapamil at all.
Type 1 diabetes is an autoimmune disease that causes loss of pancreatic beta cells, which produce endogenous insulin. To replace that, patients must take exogenous insulin by shots or pump and are at risk of dangerous low blood sugar events. There is no current oral treatment for this disease.
The suggestion that verapamil might serve as a potential Type 1 diabetes drug was the serendipitous discovery of study leader Anath Shalev, M.D., director of the Comprehensive Diabetes Center at the University of Alabama at Birmingham. This finding stemmed from more than two decades of her basic research into a gene in pancreatic islets called TXNIP. In 2014, Shalev's UAB research lab reported that verapamil completely reversed diabetes in animal models, and she announced plans to test the effects of the drug in a human clinical trial. The United States Food and Drug Administration approved verapamil for the treatment of high blood pressure in 1981.
Engineering and medical researchers at the University of Minnesota Twin Cities and Mayo Clinic have developed a new process for successfully storing specialized pancreatic islet cells at very low temperatures and rewarming them, enabling the potential for on-demand islet transplantation. The breakthrough discovery in cryopreservation is a major step forward in a cure for diabetes.
According to the Centers for Disease Control and Prevention, diabetes is the seventh leading cause of death in the United States, accounting for nearly 90,000 deaths each year. While diabetes management has improved greatly over the 100 years since the discovery of insulin, even the most modern methods remain a treatment for the condition rather than a cure.
High blood glucose is responsible for several complications in type 1 and type 2 diabetes. Researchers at Karolinska Institutet in Sweden have identified a new antidiabetic substance that preserves the activity of insulin-producing beta cells and prevents high blood glucose in mice. The study is published in the journal Science Translational Medicine.
Although several families of glucose-lowering agents are currently used in diabetes therapy, none of them can stop or reverse the progression of the disease. Maintenance of adequate beta cell activity is essential to prevent the progression of type 1 and type 2 diabetes.
"In diabetes, beta cells are challenged to produce high amounts of insulin," says the study's first author Erwin Ilegems, senior researcher at the Department of Molecular Medicine and Surgery, Karolinska Institutet. "Our study shows that this leads to a hypoxic state that increases the levels of HIF-1alpha protein, which in turn reduces beta cell activity. By treating diabetic mice with the HIF-1alpha inhibitor PX-478, we successfully decreased their blood glucose levels."
House votes to cap cost of insulin at $35
Source: ABC News
Congress could soon send to the president's desk a bill that would cap the cost of the lifesaving drug insulin at $35 per month -- a move that could significantly reduce and rein in out-of-pocket drug costs for millions of Americans with diabetes.
The House approved the bill Thursday by a vote of 232-193, with 12 Republicans joining all Democrats in support.
The bill now heads to the Senate, and it could be taken up in the upper chamber in a matter of weeks if there is bipartisan agreement.
Experts say it costs less than $10 a vial to manufacture, yet there are still American families with insurance paying hundreds of dollars per vial of insulin.
A multi-institutional team including Yale School of Medicine (YSM) has demonstrated the ability to use ultrasound to stimulate specific neurometabolic pathways in the body to prevent or reverse the onset of type 2 diabetes in three different preclinical models. The team, which includes the lab of Raimund Herzog, MD, MHS, at YSM, reported its findings in Nature Biomedical Engineering.
The team of investigators is now conducting human feasibility trials with type 2 diabetic subjects, moving medicine closer to the day when diabetes is no longer monitored and managed with blood sugar tests, insulin injections, and drug treatments. The goal of the studies is to provide a long-lasting treatment for people with type 2 diabetes to alleviate and potentially reverse the disease.
Type 2 diabetes affects millions of people worldwide. The long-term condition results in too much sugar circulating in the bloodstream. Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation.
Scientists at Nanyang Technological University, Singapore's (NTU Singapore) Lee Kong Chian School of Medicine (LKCMedicine) have mapped a novel cellular pathway that shows that saturated fat contributes to the development of diabetes and can worsen the disease, underscoring its role in metabolic diseases.
Through experiments on laboratory-cultured mouse cells and on mice fed with a diet rich in saturated fat, the NTU Singapore scientists found that saturated fatty acids can degrade a protein called FIT2, triggering a chain of molecular events that cause insulin-producing cells to lose their function and die.
When these cells die, the body's ability to secrete enough insulin in response to carbohydrates is impaired, resulting in diabetes. Partially restoring FIT2 levels in insulin-producing cells, however, could mitigate the damage caused by saturated fat, the scientists found.
The pancreas is a key metabolic regulator. When pancreatic beta cells cease producing enough insulin, blood sugar levels rise dangerously—a phenomenon known as hyperglycemia—thus triggering diabetes. After discovering that other mature pancreatic cells can adapt and partly compensate for the lack of insulin, a team from the University of Geneva (UNIGE) demonstrates that the stem cells from which beta cells are derived are only present during embryonic development. This discovery puts an end to a long-standing controversy about the hypothetical existence of adult pancreatic stem cells that would give rise to newly differentiated hormone-producing cells after birth. The scientists also succeeded in precisely defining the 'identity card' of pancreatic endocrine cells, which is a promising tool for the production of replacement insulin-secreting cells. These results can be read in Cell Reports and Nature Communications.
Genetic risk factors and diet quality are independently associated with type 2 diabetes; a healthy diet is linked to lower diabetes risk across all levels of genetic risk. That's the conclusion of a study of more than 35,000 US adults publishing April 26th in PLOS Medicine by Jordi Merino of Massachusetts General Hospital, US, and colleagues.
Both genetic and lifestyle factors are known to contribute to individual susceptibility to type 2 diabetes. Previous studies have shown that adherence to a healthy lifestyle is associated with reduced risk of type 2 diabetes across genetic profiles, but whether genetic profiles, in part, interact with lifestyle factors was unclear. In the new study, researchers analyzed data from three extensive cohort studies, including 35,759 U.S. health professionals followed for 902,386 person-years of follow-up.
The team found that, irrespective of genetic risk, a low diet quality, as compared to high diet quality, was associated with a 30% increased risk of type 2 diabetes (Pinteraction=0.69). The relative risk of type 2 diabetes was 1.29 (95% CI 1.25-1.32, P<0.001) per standard deviation increase in the global polygenic score—one measure of genetic risk—and was 1.13 (1.09-1.17, P<0.001) per 10-unit decrease in Alternate Healthy Eating Index, a measure of diet quality. The joint association of low diet quality and increased genetic risk was similar to the sum of the risk for each factor alone (Pinteraction =0.30), further supporting independent associations. That said, one limitation of the study was that the cohort sampling might not necessarily generalize to other populations.
Immune checkpoint inhibitors are widely used to treat a variety of cancers; however, one serious side effect is the onset of type 1 diabetes. Now, researchers from Osaka University have discovered that stem cell therapy may protect against such side effects.
One strategy by which tumor cells evade recognition by the immune system is by upregulating factors that interfere with immune cell signaling—a process known as immune checkpoint. For example, the upregulation of programmed death-ligand 1 (PD-L1) leads to increased binding to its receptor (PD-1) on T cells of the immune system, inhibiting T cell activation. The therapeutic use of immune checkpoint inhibitors can reverse these effects, restoring immune system surveillance and tumor cell killing. However, these anti-cancer drugs are accompanied by autoimmune side effects, including the onset of type 1 diabetes.
Type 1 diabetes is a serious autoimmune disease that develops when the level of insulin produced by the islets of Langerhans in the pancreas drops below the required threshold, resulting in the body's inability to control blood sugar levels. Such patients are dependent on insulin therapy. When insulin-producing cells are completely lost, the control of blood sugar levels becomes severely compromised, resulting in clinical complications, impaired quality of life, and a poor prognosis. Strategies for the prevention or cure of type 1 diabetes are currently lacking.
Mesenchymal stem cell (MSC) therapy is the most commonly used type of cell therapy. MSCs secrete factors that contribute to tissue regeneration, anti-fibrosis activity, and modulation of immune functions.
Islet cell transplants are a promising treatment that can cure difficult-to-treat type 1 diabetes. The cells, taken from a donor pancreas, provide patients with a sustainable and tightly controlled source of insulin. A major problem is getting the patient's immune system to accept the influx of new donor cells; the patient's protective T-cells naturally want to reject the foreign invaders.
But a team of investigators co-led by Georgia Institute of Technology researcher Andrés García overcame this hurdle in previous small animal studies. Their technique uses synthetic hydrogel particles called microgels. The microgels present a potent immunomodulatory protein called SA-FasL to modulate the body's immune response, allowing the transplanted insulin-producing cells to safely do their job, regulating blood glucose levels, and fighting diabetes.
A new study in the journal Science Advances from García and his collaborators moves this hopeful treatment strategy closer to the clinic.
"Immunosuppression is a significant problem for patients, but in our prior work we showed that this biomaterial, this microgel, is a potent immunomodulatory molecule, and can induce permanent acceptance of the new cells," said García, the Petit Chair in Bioengineering and Regents' Professor in the George W. Woodruff School of Mechanical Engineering and executive director of the Petit Institute for Bioengineering and Bioscience.
