Researchers at Oregon State University have invented a new analytical method that sheds light on an enduring mystery regarding type 2 diabetes: Why some obese patients develop the disease and others don't.
Type 2 diabetes is a serious metabolic disease that affects roughly one in 10 Americans. Formerly known as adult-onset diabetes, it is a chronic condition affecting the way the body metabolizes glucose, a sugar that's a key source of energy. This type of diabetes is frequently associated with obesity.
For some patients, that means their body does not properly respond to insulin—it resists the effects of insulin, the hormone produced by the pancreas that opens the door for sugar to enter cells. In the later disease stages, when the pancreas is exhausted, patients don't produce enough insulin to maintain normal glucose levels.
In either case, sugar builds up in the bloodstream and, if left untreated, the effect impairs many major organs, sometimes to disabling or life-threatening degrees. A key risk factor for type 2 diabetes is being overweight, often a result of eating too much fat and sugar in combination with low physical activity.
Andrey Morgun and Natalia Shulzhenko of OSU and Giorgio Trinchieri of the National Cancer Institute developed a novel analytical technique, multi-organ network analysis, to explore the mechanisms behind early-stage systemic insulin resistance.
The scientists sought to learn which organs, biological pathways and genes are playing roles.
Findings, which show that a particular type of gut microbe leads to white adipose tissue containing macrophage cells—large cells that are part of the immune system—associated with insulin resistance, were published in the Journal of Experimental Medicine.
Researchers at Oregon State University have invented a new analytical method that sheds light on an enduring mystery regarding type 2 diabetes: Why some obese patients develop the disease and others don't.
Type 2 diabetes is a serious metabolic disease that affects roughly one in 10 Americans. Formerly known as adult-onset diabetes, it is a chronic condition affecting the way the body metabolizes glucose, a sugar that's a key source of energy. This type of diabetes is frequently associated with obesity.
For some patients, that means their body does not properly respond to insulin—it resists the effects of insulin, the hormone produced by the pancreas that opens the door for sugar to enter cells. In the later disease stages, when the pancreas is exhausted, patients don't produce enough insulin to maintain normal glucose levels.
In either case, sugar builds up in the bloodstream and, if left untreated, the effect impairs many major organs, sometimes to disabling or life-threatening degrees. A key risk factor for type 2 diabetes is being overweight, often a result of eating too much fat and sugar in combination with low physical activity.
Andrey Morgun and Natalia Shulzhenko of OSU and Giorgio Trinchieri of the National Cancer Institute developed a novel analytical technique, multi-organ network analysis, to explore the mechanisms behind early-stage systemic insulin resistance.
The scientists sought to learn which organs, biological pathways and genes are playing roles.
Findings, which show that a particular type of gut microbe leads to white adipose tissue containing macrophage cells—large cells that are part of the immune system—associated with insulin resistance, were published in the Journal of Experimental Medicine.
So could gut microbes possibly treat, maybe cure, diabetes someday then?
Researchers at Karolinska Institutet in Sweden show how a molecule that they have identified stimulates the formation of new insulin-producing cells in zebrafish and mammalian tissue, through a newly described mechanism for regulating protein synthesis. The results are published in Nature Chemical Biology.
"Our findings indicate a new potential target for treating diabetes, in that we demonstrate a possible way of stimulating the formation of new insulin-producing cells," says the study's last author Olov Andersson, senior researcher at the Department of Cell and Molecular Biology at Karolinska Institutet.
Both type 1 and type 2 diabetes are characterized by raised levels of blood sugar, the result of low levels of endogenous insulin, the hormone needed for glucose uptake from the blood, or a physiological inability to utilize the insulin secreted—or both.
Researchers at Oregon State University have invented a new analytical method that sheds light on an enduring mystery regarding type 2 diabetes: Why some obese patients develop the disease and others don't.
Type 2 diabetes is a serious metabolic disease that affects roughly one in 10 Americans. Formerly known as adult-onset diabetes, it is a chronic condition affecting the way the body metabolizes glucose, a sugar that's a key source of energy. This type of diabetes is frequently associated with obesity.
For some patients, that means their body does not properly respond to insulin—it resists the effects of insulin, the hormone produced by the pancreas that opens the door for sugar to enter cells. In the later disease stages, when the pancreas is exhausted, patients don't produce enough insulin to maintain normal glucose levels.
In either case, sugar builds up in the bloodstream and, if left untreated, the effect impairs many major organs, sometimes to disabling or life-threatening degrees. A key risk factor for type 2 diabetes is being overweight, often a result of eating too much fat and sugar in combination with low physical activity.
Andrey Morgun and Natalia Shulzhenko of OSU and Giorgio Trinchieri of the National Cancer Institute developed a novel analytical technique, multi-organ network analysis, to explore the mechanisms behind early-stage systemic insulin resistance.
The scientists sought to learn which organs, biological pathways and genes are playing roles.
Findings, which show that a particular type of gut microbe leads to white adipose tissue containing macrophage cells—large cells that are part of the immune system—associated with insulin resistance, were published in the Journal of Experimental Medicine.
So could gut microbes possibly treat, maybe cure, diabetes someday then?
About 422 million people worldwide have diabetes, and 1.5 million deaths are directly attributed to diabetes each year, according to the World Health Organization. Type 1 diabetes is a chronic condition in which the insulin-producing cells in the pancreas have been damaged and no longer produce insulin; Type 2 diabetes occurs when the body becomes resistant, or insensitive, to insulin. Both versions of the disease result in elevated levels of blood glucose—or blood sugar—which can lead over time to serious damage to the heart, blood vessels, eyes, kidneys and nerves if uncontrolled by treatment. Life-saving drugs and devices have been developed for patients with diabetes, yet many people still struggle with poor blood glucose control, leaving them at high risk for complications.
Now, endocrinologists at Beth Israel Deaconess Medical Center (BIDMC) have identified a key enzyme in the synthesis of a new class of lipids (or fats), called FAHFAs, that are made in human tissues and have beneficial effects on insulin sensitivity, blood sugar control and other metabolic-related parameters in humans and mice. The discovery, published in Nature, opens the door to potential new treatments for types 1 and 2 diabetes.
In research published June 17 in the journal Science Advances, researchers in the lab of Whitehead Institute Founding Member Rudolf Jaenisch present a way to create fat cells that can be modified to display different levels of insulin sensitivity.
The cells accurately model healthy insulin metabolism, as well as insulin resistance, one of the key hallmarks of type 2 diabetes. "This system, I think, will be really useful for studying the mechanisms of this disease," said Jaenisch, who is also a professor of biology at the Massachusetts Institute of Technology (MIT).
"It's really exciting," said Max Friesen, a postdoctoral researcher in Jaenisch's lab and a first author of the study. "This is the first time that you can actually use a human stem cell-derived [fat cell] to show a real insulin response."
Body fat—also known as adipose tissue—is essential for regulating your body's metabolism and plays an important role in the storage and release of energy. When fat cells called adipocytes encounter the hormone insulin, they suck up sugar from the blood and store it for future use.
But over many years, factors such as genetics, stress, certain diets, or polluted air or water can cause this process to go awry, leading to type 2 diabetes. In this disease, adipocytes, as well as cells in the muscles and liver, become resistant to insulin and therefore unable to regulate the levels of sugar in the blood.
People with a severe form of diabetes, where the beta cells of the pancreas do not produce or no longer produce enough insulin, have no choice but to inject themselves regularly with artificial insulin in order to survive. But Insulin therapy is not without its dangers: it is difficult to dose and, in the long term, it can also lead to serious metabolic and cardiovascular problems. Scientists at the University of Geneva (UNIGE) have been working for several years on an alternative therapy based on the S100A9 protein. They have now provided proof of principle that this protein can significantly improve metabolism in insulin deficiency. In addition, by deciphering the biological mechanisms at work, they have discovered a previously unknown anti-inflammatory effect that could prove key well beyond diabetes. These results are published in the journal Nature Communications.
Insulin therapy, which celebrated its 100th anniversary in 2021, has probably saved the lives of hundreds of millions of people suffering from type 1 diabetes or severe forms of type 2 diabetes. However, it has some risks, if the doses are too high or too low, and is even directly responsible for some potentially fatal conditions. Consequently, the life expectancy of insulin-dependent diabetics is reduced by 10 to 15 years compared to the norm. "Life-threatening hypoglycemia, negative impact on fat metabolism and increased cholesterol: these are some severe side effects of insulin. This is why we are looking to develop complementary or alternative treatments that are more effective and less dangerous," says Roberto Coppari, a professor in the Department of Cell Physiology and Metabolism and Coordinator of the Diabetes Center of UNIGE Faculty of Medicine, who directed this work.
In type 1 diabetes, the body develops immune cells that target pancreatic beta cells, which play a critical role in the production and secretion of insulin. One of the earliest targets of this immune response is a specific sequence of amino acids, or peptide, within the insulin molecule. What triggers this autoimmune response remains unknown.
Now, researchers at Joslin Diabetes Center and Boston College have identified a species of human gut bacterium that makes a protein containing a sequence of amino acids that mimics the insulin peptide targeted by the immune system in type 1 diabetes. Analysis revealed that the immune cells that target the insulin peptide in type 1 diabetes cross-react with the similar sequence from the gut bacterial peptide, and that the presence of this bacterium can accelerate onset of diabetes in a mouse model of type 1 diabetes. More importantly, further investigation also revealed a link between the presence of the gut bacterium and the development of type 1 diabetes in children at genetic risk of this disease. The findings are published in PNAS.
In a potential game changer for patients with type 2 diabetes, a team of researchers at the Diabetes, Obesity, and Metabolism Institute (DOMI) at the Icahn School of Medicine at Mount Sinai has identified a therapeutic target for the preservation and regeneration of beta cells (β cells)—cells in the pancreas that produce and distribute insulin. The discovery could prevent insulin resistance and thus have significant benefits for millions of people worldwide. The results of the study were published in Nature Communications in July.
All major forms of diabetes are caused by insufficient β-cell mass. When blood glucose levels rise in the body, such as in response to a high-fat diet, β cells respond by producing and releasing more insulin to bring blood glucose levels under control. But prolonged high blood glucose, known as hyperglycemia, can impair the ability of β cells to produce and secrete insulin. This results in a vicious cycle of ever-increasing glucose levels and ever-declining β-cell function, leading to β-cell death—a phenomenon known as glucose toxicity. Thus, preservation and regeneration of β cells is a therapeutic goal for diabetes.
The Mount Sinai research team found a molecular mechanism that appears to be involved in β-cell preservation and regeneration involving carbohydrate response-element binding protein (ChREBP). The researchers showed that production of a hyperactive isoform of this protein, ChREBPβ, is necessary to produce more β cells in response to an increased demand for insulin in the body due to a high-fat diet or significant glucose exposure. However, prolonged, increased glucose metabolism can result in a vicious cycle in which ChREBPβ is overproduced, resulting in glucose toxicity in the β-cells and their subsequent death.
In a multi-site study of medical records, researchers at Johns Hopkins Children's Center and across the United States say they have documented a steep rise in type 2 diabetes among children during the COVID-19 pandemic.
In a report on the findings, published Aug. 17 in The Journal of Pediatrics, the investigators note it is unclear whether the virus infection itself was a factor in the rise, and they point to the switch to virtual learning and shutdown of sports and school activities as "environmental factors" that likely increased risk.
Before the pandemic, type 2 diabetes was increasing among children around the world, and because rates of childhood diabetes are known to rise and fall over time, the investigators launched a nationwide review of medical records to assess the impact of the pandemic, according to Sheela N. Magge, M.D., M.S.C.E., director of the Division of Pediatric Endocrinology at the Children's Center.
A new study published in Cell Chemical Biology describes an alternative approach to treat diabetes by identifying drugs directly increasing the number of incretin-expressing cells. The work results from researchers at Karolinska Institutet.
"We have previously performed unbiased small molecule screens for novel potential ways of treating diabetes by targeting the insulin-producing beta-cells. However, what I think is exciting with this work is that we leveraged our unique in vivo drug-discovery approach to a different organ and enteroendocrine cells, which also have the potential to improve management of diabetes," says principal researcher Olov Andersson from the Department of Cell and Molecular Biology.
Hormones released from the gut have important roles in modulating satiety, insulin secretion and blood glucose levels. Of relevance to diabetes, the incretins are hormones secreted upon food intake to enhance insulin secretion and reduce blood glucose levels. There are two different incretins that are called GIP and GLP-1. To identify small molecules that directly increase the number of incretin-expressing cells, the researchers established a high-throughput in vivo chemical screen by measuring the amount of GIP in zebrafish. Several of the identified drug candidates increase the number of incretin-expressing cells and improve glucose control in both zebrafish and diabetic mice.
A team of researchers from Helmholtz Munich, the German Center for Diabetes Research (DZD) and Novo Nordisk have developed a new hormone combination for the future treatment of type 2 diabetes. The scientists have combined the blood sugar-reducing effects of the drugs tesaglitazar and GLP-1 (Glucagon-like peptide-1) in a new and highly effective drug. The advantage is that, by combining tesaglitazar with GLP-1, the tesaglitazar only enters tissue that contains GLP-1 receptors. This reduces the adverse effects of tesaglitazar while increasing the effects on sugar metabolism. The new drug has already been successfully tested in animal studies. The findings were published in Nature Metabolism.
The drug tesaglitazar improves glucose and fat metabolism in patients with type 2 diabetes. It acts on two receptors within the cell nucleus to increase insulin sensitivity. This was proven in phase 3 clinical trials. However, tesaglitazar also caused unwanted effects, such as signs of kidney damage. Nevertheless, in order to use the drug therapeutically, the researchers used a trick: They biochemically combined tesaglitazar with the gastrointestinal hormone GLP-1, which since several years successfully used to treat type 2 diabetes. This allows the combined drug to only act on cells and tissue that contain GLP-1 receptors.
"This trick enabled us to combine the blood sugar-reducing effects of GLP-1 and tesaglitazar into a single highly effective molecule, while keeping tesaglitazar away from tissues that it could damage," explains PD Dr. Timo Müller, corresponding author, director of the Institute of Diabetes and Obesity, and scientist at DZD.
A team of University of British Columbia researchers working on developing oral insulin tablets as a replacement for daily insulin injections have made a game-changing discovery.
Researchers have discovered that insulin from the latest version of their oral tablets is absorbed by rats in the same way that injected insulin is.
"These exciting results show that we are on the right track in developing an insulin formulation that will no longer need to be injected before every meal, improving the quality of life, as well as mental health, of more than nine million type 1 diabetics around the world," says professor Dr. Anubhav Pratap-Singh, the principal investigator from the faculty of land and food systems.
He explains the inspiration behind the search for a non-injectable insulin comes from his diabetic father who has been injecting insulin 3-4 times a day for the past 15 years.
Researchers from Children's Hospital of Philadelphia (CHOP) have used advanced three-dimensional mapping techniques at a microscopic level to identify a multitude of genetic variants and corresponding target gene pairings in the pancreas that are implicated in type 2 diabetes. In addition to these discoveries, the resulting datasets will serve as a key resource for researchers all over the world to delve deeper into the genetic origins of type 2 diabetes and further explore the roles of different types of cells in the development of the disease.
The findings were published today in the journal Cell Metabolism.
Type 2 diabetes cases are on the rise and being diagnosed in patients earlier in life than what has been historically observed. However, while many cases can be attributed to a rise in obesity and sedentary lifestyle, increasing evidence suggests a strong role that genetic risk factors play in this relatively common disease. Prior genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with an increased risk of developing type 2 diabetes.
New York governor declares disaster emergency after polio found in wastewater
Source: Reuters
Sept 9 (Reuters) - New York Governor Kathy Hochul declared a state disaster emergency on Friday after samples of the polio virus were discovered in wastewater in three counties outside of New York City.
Hochul's executive order came more than a month after an adult in Rockland County, north of New York City, was diagnosed with the disease in July. It was the first confirmed case of polio in the United States in nearly a decade.
The declaration would expand the number of people authorized to administer polio vaccines and other steps to accelerate inoculation rates. The state of emergency will stay in effect until October 9. The polio virus was present in wastewater samples collected as early as April, Hochul's executive order said.
Virus was detected in wastewater samples taken in Orange, Rockland and Sullivan counties every month since April, indicating the virus was present in the state before the Rockland County case was found in July.
Like all living beings, human physiological processes are influenced by circadian rhythms. The disruption of our internal clocks due to an increasingly unbalanced lifestyle is directly linked to the explosion in cases of type 2 diabetes. Now, a team from the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG), in Switzerland, has found that his disturbance disrupts the metabolism of lipids in the cells that secrete glucose-regulating hormones. Sphingolipids and phospholipids, lipids located on the cell membrane, seem to be particularly affected. This change in lipid profiles then leads to a rigidity of the membrane of these cells. These results, appearing in the journal PLOS Biology, provide further evidence of the importance of circadian rhythms in metabolic disorders.
Lipids have a variety of cellular functions. As one of the main components of cell membranes, they are involved in the signaling pathways through which cells communicate with each other and with their environment. "We have known for some time that the disruption of circadian clocks was closely linked to metabolic diseases, such as type 2 diabetes, where the body is no longer able to regulate blood sugar levels effectively," explains Charna Dibner, a professor in the Departments of Surgery and of Cellular Physiology and Metabolism, as well as in the Diabetes Center of the UNIGE Faculty of Medicine and the HUG, who led this research. "It is also established that lipids play a significant role in metabolic disorders. But the impact of circadian rhythms on lipid functions remained unknown."
Children who were infected with COVID-19 show a substantially higher risk of developing type 1 diabetes (T1D), according to a new study that analyzed electronic health records of more than 1 million patients ages 18 and younger.
In a study published today in the journal JAMA Network Open, researchers at the Case Western Reserve University School of Medicine report that children and adolescents who contracted COVID-19 were more prone to developing T1D in the six months following their COVID diagnosis.
The findings showed a 72% increase in new diagnoses of T1D in COVID-19 patients 18 years old and younger—although the research emphasized that it is unclear whether COVID-19 triggers new onset of T1D.
About 187,000 children and adolescents younger than 20 live with T1D nationally, according to the Centers for Disease Control and Prevention (CDC).
Using state of the art techniques, researchers from Uppsala University have shown that the metabolism in patients with type 2 diabetes and prediabetes was much more disturbed than previously known, and that it varied between organs and severity of the disease. The study is a collaboration with e.g. Copenhagen University and AstraZeneca and it has been published in the journal Cell Reports Medicine.
The most typical alterations in people with type 2 diabetes are insufficient secretion of insulin and reduced sensitivity to insulin in different organs. To examine what happens in these organs when type 2 diabetes develops, the researchers in the current study have studied proteins both in the cell islets in the pancreas where insulin is produced, and in the main tissues that insulin acts on, namely the liver, skeletal muscle, fat and blood.
Diabetes and prediabetes
The researchers compared proteins in samples from people with type 2 diabetes, prediabetes, i.e. a stage before fully developed type 2 diabetes, and without any diabetes. The results showed far more disturbances in different metabolic pathways than previously known. There was also a correlation between the alterations and the different stages of the disease.
"We detected many protein levels that were either higher or lower than normal in tissues from people at different stages of disease. People with prediabetes displayed major alterations that are associated with inflammation, coagulation and the immune system in the pancreatic islets. In fully developed type 2 diabetes there were more wide-spread abnormalities, for example in lipid and glucose metabolism and in energy production in liver, muscle and fat," says Professor Claes Wadelius, who coordinated the study.
The most extensive image bank of samples of the pancreas from children who developed diabetes shortly before death has gone live at Vanderbilt University Medical Center, with the aim to advance global medical research in the diabetes field.
The University of Exeter and Vanderbilt University Medical Center (VUMC) teamed up to make high-resolution images of pancreatic tissue available in Pancreatlas, the world's first on-line imaging database of human pancreatic tissue created and housed at VUMC.
The pancreas contains the beta cells that produce the insulin that controls blood sugar and because of this is implicated in diseases such as diabetes. The image bank is a valuable asset to researchers because the human pancreas cannot be safely biopsied, and study of the cellular changes that cause type 1 diabetes can only be undertaken in pancreas specimens from individuals with the disease following their death.
People of South Asian ethnicity may be able to achieve type 2 diabetes remissions by following a structured weight management program, according to a new study which saw one third of participants lose more than 10% of their body weight.
The findings from the STANDby trial—led by the University of Glasgow and published in The Lancet Regional Health—Southeast Asia—used a formula diet as "total diet replacement" for up to 12 weeks in people of South Asian ethnicity, and found sufficient weight loss was achieved by around 40% of all participants to allow for remission of their type 2 diabetes.
Globally, type 2 diabetes (T2D) affects over 400 million people, and almost 4 million, or one in ten adults in the UK.
Around one in four people worldwide are of South Asian origin, with considerably higher risk of T2D than the general UK/European white population, developing the condition at a lower body mass index and at younger ages.
Recent work from the DiRECT study, also led by the University of Glasgow, has shown how weight loss of 10 kg or more, using an evidence-based weight management program called "Counterweight-Plus," resulted in remission of diabetes after one year, in 70% of people with diagnosed T2D of less than six years' duration. Almost half (46%) of all participants in the DiRECT study achieved remission. However, in DiRECT, almost all participants were white British, so more research was required to understand its implications in other ethnic groups.