Tag: diabetes

Categories : Metabolic DisordersTags :

Newly Discovered Hormone Implicated in Development of Diabetes

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A newly discovered hormone named fabkin helps regulate metabolism and may play an important role in the development of both type 1 and type 2 diabetes, according to a new study published in Nature.

Fabkin levels were abnormally high in mice and human patients with either type 1 or type 2 diabetes, and blocking the activity of fabkin prevented the development of both forms of diabetes in the animals. Fabkin likely plays a similar role in humans and the hormone complex could be a promising therapeutic target, according to the researchers.

“For many decades, we have been searching for the signal that communicates the status of energy reserves in adipocytes to generate appropriate endocrine responses, such as the insulin production from pancreatic beta cells,” said senior author Gökhan S. Hotamisligil. “We now have identified fabkin as a novel hormone that controls this critical function through a very unusual molecular mechanism.”

Many hormones are involved in the regulation of metabolism, such as insulin and leptin. Fabkin is different from traditional hormones in that it is not a single molecule with a single defined receptor. Instead, fabkin is composed of a functional protein complex consisting of multiple proteins, including fatty acid binding protein 4 (FABP4), adenosine kinase (ADK) and nucleoside diphosphate kinase (NDPK). Through a series of experiments, the researchers determined that fabkin regulates energy signals outside of cells. These signals then act through a family of receptors to control target cell function. In the case of diabetes, fabkin controls the function of beta cells in the pancreas that are responsible for insulin production.

Hotamisligil and colleagues previously discovered that a protein known as FABP4 is secreted from fat cells during lipolysis, the process in which lipids stored within fat cells are broken down, typically in response to starvation. Since then, many studies showed links between circulating FABP4 and metabolic diseases including obesity, diabetes, cardiovascular disease, and cancer. However, the mechanism of action was unknown.

In the new study, the researchers showed that when FABP4 is secreted from fat cells and enters the bloodstream, it binds with the enzymes NDPK and ADK to form the protein complex now identified as fabkin. In this protein complex, FABP4 modifies the activity of NDPK and ADK to regulate levels of molecules known as ATP and ADP, which are the essential units of energy in biology. The researchers discovered that surface receptors on nearby cells sense the changing ratio of ATP to ADP, triggering the cells to respond to the changing energy status. As such, fabkin is able to regulate the function of these target cells.

The pancreas’ beta cells are a target of fabkin and the hormone is a driving force behind the development of diabetes, the researchers showed. When fabkin in mice was neutralised with an antibody, the animals did not develop diabetes. When the antibody was given to obese, diabetic mice, they reverted to a healthy state.

“The discovery of fabkin required us to take a step back and reconsider our fundamental understanding of how hormones work.” said lead author Kacey Prentice. “I am extremely excited to find a new hormone, but even more so about seeing the long-term implications of this discovery.”

Source: Harvard University

Categories : CancerTags :

Anti-diabetes Drug under Development May Also Treat Breast Cancer

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Source: NCI

A new study has shown that a small molecule inhibitor drug, with the unwieldy designation of PF05175157, originally developed to treat diabetes by Pfizer, may help in the treatment of breast cancer by blocking a key enzyme. 

The findings from the Yale Cancer Center-led study were reported at the 2021 San Antonio Breast Cancer Symposium in San Antonio, Texas.

“Our research shows the preclinical, anti-cancer activity using PF05175157 may lead us to bring this drug back into the clinic to help treat patients with breast cancer,” said lead study author Julia Foldi, MD, PhD, a clinical fellow at Yale Cancer Center and Smilow Cancer Hospital. “More studies are needed, but our initial data looks very promising.”

Cancer cells are characterised by altered metabolism. In this study, the Yale team identified new metabolic vulnerabilities in cancer cells that are based on a loss of enzyme diversity. They found that an enzyme called acetyl-CoA-carboxylase-1 (ACC1), is critical for the survival of breast cancer cells. The ACC1 enzyme is the key initial step in fatty acid synthesis. Fatty acids are building blocks of the various types of lipids and fat that are the critical ingredients of cell membranes and play an important role in energy generation in cells. The team’s analysis demonstrated that blocking ACC1 using PF05175157 can inhibit the growth of breast cancer cells grown in mice and also in patient-derived cancer models.

“We are currently testing this drug in combination with other approved breast cancer drugs to see if it could improve their activity, with the hope to bring the most promising combinations to the clinic to help patients with breast cancer,” added Lajos Pusztai, MD, DPhil, Professor of Medicine (Medical Oncology), Director of Breast Cancer Translational Research at Yale Cancer Center, and senior author of the study.

Source: Yale Cancer Center

Categories : Metabolic DisordersTags :

A Needle-free Way of Blood Glucose Monitoring

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In order to find an alternative to lancets for blood glucose monitoring, researchers applied needle-free jet injection, an emerging but well-developed technique in which a drug is delivered directly with a high-speed narrow jet of fluid.

The study, led by ABI researchers Jiali Xu and James McKeage, demonstrated for the first time that a jet injector could also be used to collect blood samples from humans – that is, release enough blood for glucose sampling, sans needles. The findings appear in the Journal of Diabetes Science and Technology.

Fingertips are the preferred site for blood sampling because they have a high density of blood vessels, they are also sensitive, and pain, skin damage, bruising and risk of infection from regular ‘pricking’ has spurred increasing efforts to develop needle-free methods of blood testing for people with diabetes.

Jet injection, which does not rely on a needle, is an appealing alternative. Jiali Xu of the Auckland Bionengineering Institute (ABI) and her team demonstrated that the technology, using electric motors rather than the standard mechanical spring, could also be used to pierce the skin with a small volume of harmless saline solution, releasing enough blood for glucose concentration measurement.

The study involved 20 healthy participants, each of which received a lancet prick and jet injection on four fingertips through three differently shaped and sized nozzles. “Which were designed to mimic the wound left from a lancet prick, in the anticipation that it might release blood in a way similar to a lancet prick,” said Ms Xu.

Some nozzle shapes performing better than others – a ‘slot’ shaped nozzle released more blood than a circle-shaped nozzle, for instance.

Most of the different jet injection nozzles were generally perceived by the participants, who were unable to see the injections, as no more painful than a standard lancet, and in some cases, less so. A questionnaire was given 24 hours later to assess pain, swelling and bleeding.

People with diabetes may find jet injection more acceptable than using a needle, but the researchers caution against jumping to conclusions. “When you know there’s not a device that is pricking your skin, you could speculate that people will find jet injection more acceptable,” says Professor Andrew Taberner, head of the Bioinstrumentation Lab at the ABI, and Ms Xu’s supervisor. “But we don’t have evidence to back that up. That wasn’t part of this study. We were first trying to find out if it worked, and it did.”

He was pleased, but not surprised. “Diesel mechanics have known for years that you should never put your finger in front of a fuel injector, because it will inject fuel into your finger. They found this out the hard way. But we’re taking advantage of what diesel mechanics discovered accidentally years ago, with a very small amount of harmless liquid, to deliberately release blood.”

The team is now trying to see if they can also extract blood with this technology, allowing for the design of an even smaller nozzle.

Moreover, “our technology has the capability to both deliver and withdraw fluid. No other jet projection technology has that capacity,” said Dr Taberner.

Development and commercialisation of the technology will take time but he believes Ms Xu’s research will contribute to the ultimate aim, of the development of a single lancet-free reversible technology that will allow for both blood sampling and insulin delivery based on the glucose measurement in one device.

“I hope that this research will contribute to that, and the improvement in human healthcare, especially in the management of diabetes,” said Ms Xu.

Source: University of Auckland

Categories : Medical Research & TechnologyTags :

Scientists Discover a New Sense for Sugars

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In a study published in PLOS ONE, scientists report the identification of a new human sensory ability to detect sugars in the mouth with a kind of a molecular ‘calorie detector’. It could help explain why artificially sweetened beverages just don’t have the same appeal as ones containing sugar.

“Our mouth can identify when a sweetener has the potential to deliver calories versus a non-caloric sweetener, which cannot,” said first author Paul Breslin, PhD, a Monell investigator and a professor of Nutritional Sciences at Rutgers University.

The paper describes the first-in-human demonstration of a signaling pathway that uses the sugar glucose, a component of table sugar and high fructose corn syrup, to signal the presence of calories, in addition to the well-studied sweet-taste receptor in taste buds. Glucose is present in many foods, and has been consumed by humans in the form of honey, fruit and other sugar-rich foods.

“Humans love fruit and sugar, as do many other apes, which obtain most of their calories from sugar,” said Prof Breslin.

Recent findings from Monell showed taste bud cells in mice could identify when a sweetener has calories to burn, which prompted the researchers to see whether the ability to sense glucose in the human mouth may also involve this additional pathway. The team wanted to know if the calorie detector is functional, and if it could affect our responses to dietary sugar.

“Now that we know this calorie-detecting taste system is operating in humans, it could help explain the overall preference for sugared beverages over non-caloric sweetener beverages,” said Prof Breslin.

In a series of three human-taste experiments, the team compared oral glucose sensitivity to the ability to sense the artificial sweetener sucralose and to a special form of glucose that cannot be metabolised. “Overall, there are two sweet-sensing pathways in the mouth: one for sweet taste, and another for detecting potential energy-burning sugars,” said coauthor Linda J. Flammer, PhD, a senior research associate at Monell.

The fact that diet fizzy drinks never captured a major share of the beverage market always puzzled Prof Breslin, but he now has a hint: “Diet drinks are not as satisfying as sugared beverages. As a public health initiative, might we get beverages and foods with lower sugar levels to be more rewarding? Now that we know there is this second glucose-sensing system in the mouth, maybe we can tap into it to make healthier beverages that people enjoy drinking.”

Sugar calories are sensed in the gut and blood after swallowing, but this study shows that sugars are identified as different from non-caloric sweeteners in the mouth. “It is remarkable that we evolved a mechanism not only to taste oral sugars as sweet, but also to sense that they have a metabolic or caloric signal,” said Breslin. “This means that the mouth is much smarter than we realised and that it will be difficult to trick it by simply providing non-caloric sweeteners.”

Source: Monell Chemical Senses Center

Categories : COVIDTags :

More ACE2 Makes Pancreatic Cells a COVID Target

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Source: CDC

Researchers have revealed insights into how SARS-CoV-2 attacks the insulin-producing cells of the pancreas.

There is mounting evidence of damage to the pancreas and resulting diabetes attributed to COVID, which is of great concern. The virus targets the angiotensin converting enzyme 2 (ACE2) protein on the surface of those cells, and is the subject of a special presentation at this year’s Annual Meeting of the European Association for the Study of Diabetes, given by the University of Siena’s Professor Francesco Dotta. 

“The SARS-CoV-2 virus attacks specific host tissues because of the presence of viral receptors on the surface of the target cells. As such, virus binding to ACE2 protein is the key determinant for its entry, propagation and transmissibility,” explained Prof Dotta.

“Multiple studies have shown that older adults and those with chronic medical conditions like heart and lung disease and/or diabetes are at the highest risk for complications from SARS-CoV-2 infections. Moreover, impaired blood sugar control is associated with increased risk of severe COVID, suggesting a link between COVID infection and diabetes. Several reports indicate a wide, although variable, distribution of the ACE2 protein among different tissues.”

Prof Dotta and colleagues studied the ACE2 expression pattern in pancreatic tissue samples of non-diabetic multiorgan donors to better understand the molecular link between COVID and diabetes.

In the ‘normal’ pancreas, ACE2 is highly expressed in microvasculature and in ductal cells. “Importantly, we found that ACE2 was expressed in human pancreatic islets, where it is preferentially expressed in insulin producing beta-cells. We also demonstrated that ACE2 levels were increased under pro-inflammatory conditions, thus confirming the link between inflammation and ACE2 also in pancreatic islet beta cells.”

In order to isolate the mechanism involved in the upregulation of ACE2 induced by inflammation, ACE2 levels were measured in human pancreatic islets pre-treated with Jak1/2 and TYK2 inhibitors, which block inflammation in beta cells, and then exposed to pro-inflammatory conditions. 

Prof Dotta said: “We showed that these drugs prevent the ACE2 increase induced by inflammation in human pancreatic islets, demonstrating that SARS-CoV-2 receptor ACE2 is regulated through specific molecular pathways and that its increased expression can be prevented.

“We studied the mechanisms of SARS-CoV-2 virus entry into insulin producing beta cells and we discovered that these cells express the SARS-CoV-2 receptor ACE2.” Other authors have independently confirmed such data.

Of note, additional published data confirmed that SARS-CoV-2 can indeed infect pancreatic insulin-producing cells causing their dysfunction or death. Moreover, during inflammation, ACE2 expression increases several times above standard values.

Prof Dotta concluded: “This means that these insulin-producing beta cells could be even more susceptible to viral infection when inflamed. This finding is also important from a clinical standpoint, since keeping inflammatory status under control in patients with COVID may reduce the expression of ACE2 receptor in beta cells with beneficial effects on blood sugar and metabolic control of patients.”

Source: EurekAlert!

Categories : Diseases, Syndromes and Conditions UncategorizedTags :

Diabetes Drug Could Halve Glaucoma Risk

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GLP-1R agonists, a popular class of diabetes drugs, may also have a protective effect against glaucoma in diabetic patients, according to a new study published in the British Journal of Ophthalmology.

The researchers examined retrospective data of 1961 diabetic patients who were new users of this class of drugs and matched them to 4371 unexposed control subjects. After 150 days on average, 10 patients in the medicated group were newly diagnosed with glaucoma (0.5%) compared to 58 patients (1.3%) in the control group. These results indicate that GLP-1 receptor agonists could halve a diabetic patient’s risk of developing glaucoma.

The findings are supported by a Penn Medicine study from 2020, which found that GLP-1R agonists reduced neuroinflammation and prevented retinal ganglion cell death in mice. This class of drugs has also shown similarly protective effects against Alzheimer’s and Parkinson’s diseases in animal models, and clinical trials are underway to test the medications against neurodegenerative diseases in humans.

Glaucoma is the second leading cause of blindness worldwide, and people with diabetes are twice as likely to develop the condition.

“It was very encouraging to see that a popular diabetes medication could significantly reduce the risk of developing glaucoma, and our study suggests that these medications warrant further study in this patient population,” said Qi N. Cui, MD, PhD, with Brian VanderBeek, MD, MPH, both assistant professors of Ophthalmology at Penn.

Source: EurekAlert!

Categories : Medical Research & Technology Metabolic DisordersTags :

An Oxygen-delivering Hydrogel for Diabetic Foot Ulcers

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Photo by Denes Kozma on Unsplash

A quarter of people with diabetes develop foot ulcers, which are slow to heal due to hypoxic conditions in the wound from impaired blood vessels and increased inflammation. These wounds can become chronic, leading to poor quality of life and possibly amputation.

Jianjun Guan, professor of mechanical engineering and materials science at the McKelvey School of Engineering at Washington University in St. Louis, has developed a hydrogel that delivers oxygen to a wound and decreases inflammation, helps to remodel tissue and speeds up healing. The results are published in Science Advances. 

Prof Guan’s new hydrogel uses microspheres to gradually release oxygen to interact with the cells by means of an enzyme coating that converts the microsphere’s contents into oxygen. In this way, the hydrogel delivers oxygen over two weeks, reducing inflammation and promoting healing.
“The oxygen has two roles: one, to improve skin cell survival under the low-oxygen condition of the diabetic wound; and two, oxygen can stimulate the skin cells to produce growth factors necessary for wound repair,” Prof Guan said.

Source: Washington University in St. Louis

Categories : Gender Metabolic DisordersTags :

Australian Women with Diabetes Incur Significant Expenses

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A new study from at the University of Technology Sydney (UTS) and the University of South Australia has found that women with diabetes incur significant out-of-pocket expenses in managing their health, with costs rising as the disease continues.

Researchers found middle-aged and older women spend almost $500 a year from their own funds, visiting a diverse range of health services to manage their diabetes. Their findings were published in the journal PLOS One.

“Our findings were that most women (88.3 per cent) consulted at least one health care practitioner in the previous 12 months for their diabetes, including medical doctors, allied health practitioners and complementary medicine practitioners, spending on average $492.60 per woman a year,” said Distinguished Professor Jon Adams, deputy head of the School of Public Health at UTS.

He continued: “Our analysis suggests approximately $252 million is spent annually on out-of-pocket expenditure for diabetes management by Australian women aged 50 years and over. The results of this study provide important insights regarding public and private health care use by middle-aged and older Australian women living with diabetes.”

The economic burden these women are placed under warrants further investigation to understand how health care services (and the integration of such services) can better address their biopsychosocial needs, the researchers said.

However, the researchers said the economic burden of self-care of chronic illness by individuals and households is often overlooked in Australia in favor of analyses that center on the macro-economy and the cost to the Australian government.

Diabetes mellitus is a disease of inadequate control of blood levels of glucose. Type 1 and 2 diabetes are the main subtypes, each with different pathophysiology, presentation, and management, but both have a potential for hyperglycaemia. Poor management of diabetes can lead to other chronic health problems such as increased cardiovascular disease risk. 

Source: University of Technology Sydney (UTS)

Categories : Metabolic DisordersTags :

A Specific Type of Fat Cell Responds to Insulin

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Source: Pixabay

While it was known that fat cells can influence insulin sensitivity, researchers have recently discovered that there are three different subtypes of mature fat cells in white adipose tissue and that it is only one of these, called AdipoPLIN, that responds to insulin. The findings, which were published in Cell Metabolism, may have implications for the treatment of metabolic diseases such as Type 2 diabetes. 

“These findings increase our knowledge about the function of fat tissue,” said co-corresponding author Niklas Mejhert, researcher at the Department of Medicine, Huddinge, at Karolinska Institutet. “They show that the overall capacity of fat tissue to respond to insulin is determined by the proportion and function of a specific fat cell subtype. This could have implications for diseases such as obesity, insulin resistance and Type 2 diabetes.”

The researchers identified 18 classes of cells that form clusters in white adipose tissue in humans. Of these, three constituted mature fat cells with distinct phenotypes.

To determine if a specific function was linked to the fat cell subtypes, the researchers measured how these subtypes in four people reacted to short-term increases in insulin levels. They found that insulin activated the gene expression in the AdipoPLIN subtype but did not affect the other two subtypes. The response to insulin stimulation was also proportional to the individual’s whole-body insulin sensitivity.

A challenge to the prevailing view
“Our findings challenge the current view of insulin resistance as a generally reduced response to insulin in the fat cells,” said co-corresponding author Mikael Rydén, professor in the same department. “Instead, our study suggests that insulin resistance, and possibly type 2 diabetes, could be due to changes in a specific subtype of fat cells. This shows that fat tissue is a much more complex tissue than previously thought. Like muscle tissue, people have several types of fat cells with different functions, which opens up for future interventions targeted at different fat cell types.”

The researchers employed spatial transcriptomics, which generates information about tissue organisation via microscopy and gene expression via RNA sequencing.

”This study is unique in that it is the first time we’ve applied spatial transcriptomics to fat tissue, which has a special set of characteristics and composition,” said third corresponding author Patrik Ståhl. “We are very happy that the technology continues to contribute to solving biologically complex questions in an increasing number of research areas.”

Source: Karolinska Institute

Categories : Diet and Nutrition Metabolic DisordersTags :

Low GI Diet Has Noticeable Benefit against Diabetes

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Following a low glycaemic diet confers small but important benefits in blood glucose levels, cholesterol, weight and other risk factors, according to a study published by The BMJ.

The improvements were over and above existing drug and insulin therapy, suggesting this diet may help complement treatment, said the researchers.

Research has shown that foods with a low glycaemic index (GI), which is a measure of how quickly a food affects blood glucose levels relative to white bread, can help keep blood sugar levels steady and reduce the risk of heart disease in people with diabetes. These include foods such as vegetables, most fruits, pulses and wholegrains.

Due to this, clinical guidelines across the world recommend a low GI or GL (glycaemic load) diet for people with diabetes. However, the last European Association for the Study of Diabetes (EASD) guidelines were released over 15 years ago and since that time a number of trials have been published.
So researchers set out to summarise the effect of low GI/GL dietary patterns on blood sugar control and other known risk factors in diabetes to help inform the update of the EASD guidelines for nutrition treatment.

Their results are based on 27 randomised controlled trials published up to May 2021 investigating the effect of diets with low GI/GL in diabetes for three or more weeks.

The trial recruited a total of 1617 participants with type 1 or 2 diabetes, who were predominantly middle aged, overweight or obese with moderately controlled type 2 diabetes treated with drugs or insulin.

Though the trials varied quality, the researchers could assess the certainty of evidence using the recognised GRADE system.

The results show that low-GI/GL dietary patterns were linked to small but clinically meaningful reductions in blood sugar levels (HbA1c) compared with higher-GI/GL control diets.

Some other risk factors saw changes, such as fasting glucose (blood sugar levels after a period of fasting), LDL cholesterol, body weight, and C-reactive protein (a chemical associated with inflammation), but not blood insulin levels, HDL cholesterol, waist circumference, or blood pressure. The certainty of evidence was high for reduction in blood sugar levels and moderate for most other outcomes.

Limitations that included imprecision in the evidence for the effect of low GI/GL dietary patterns on LDL cholesterol and waist circumference, and the small number of available trial comparisons for blood pressure and inflammatory markers.

However, they say their findings show that low GI/GL dietary patterns “are considered an acceptable and safe dietary strategy that can produce small meaningful reductions in the primary target for glycaemic control in diabetes, HbA1c, fasting glucose, and other established cardiometabolic risk factors.”

“Our synthesis supports existing recommendations for the use of low GI/GL dietary patterns in the management of diabetes,” they concluded.

Source: MedicalXpress