Tag Archives: #glucose

Different Forms of Sugar Impact Hunger-suppressing Hormones in Young Adults (Biology)

Study highlights how the body reacts to sucrose vs. glucose.

Drinks with sucrose compared to glucose may cause young adults to produce lower levels of appetite-regulating hormones, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

Too much sugar consumption is a contributing factor for obesity. Sucrose, or “table sugar,” is composed of equal parts glucose and fructose and is often added to processed foods like soda, candy, cereal and canned foods. Glucose can be found in foods like honey and dried fruits.

“Our study found that when young adults consumed drinks containing sucrose, they produced lower levels of appetite-regulating hormones than when they consumed drinks containing glucose (the main type of sugar that circulates in the bloodstream),” said study author Kathleen Page, M.D., of the USC Keck School of Medicine in Los Angeles, Calif. “This study is the first to show how individual characteristics, including body weight, sex and insulin sensitivity, affect hormone responses to two different types of sugar, sucrose and glucose. These findings highlight the need to consider how individual characteristics affect the body’s responses to different types of sugar and other nutrients in our food supply.”

The researchers studied 69 young adults between the ages of 18-35 years old who participated in two study visits where they consumed drinks containing either sucrose or glucose. They found that when the young adults consumed drinks containing sucrose, they produced lower amounts of hormones that suppress hunger compared to when they consumed drinks containing an equal dose of glucose. They also found that individual characteristics, including body weight and sex, affected the hormone responses to the different sugars.

Other authors of the study include: Alexandra G. Yunker, Sabrina Jones, Brendan Angelo, Alexis DeFendis and Trevor A. Pickering of the USC Keck School of Medicine; Shan Luo, Hilary M. Dorton and Jasmin M. Alves of the USC Keck School of Medicine and the University of Southern California in Los Angeles, Calif.; and John R. Monterosso of the University of Southern California.

The manuscript received funding from the National Institute of Diabetes and Digestive and Kidney Diseases and the Southern California Clinical and Translational Science Institute.

Reference: Alexandra G Yunker, Shan Luo, Sabrina Jones, Hilary M Dorton, Jasmin M Alves, Brendan Angelo, Alexis DeFendis, Trevor A Pickering, John R Monterosso, Kathleen A Page, Appetite regulating hormones are reduced after oral sucrose vs glucose: influence of obesity, insulin resistance and sex, The Journal of Clinical Endocrinology & Metabolism, , dgaa865, https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgaa865/6017471?redirectedFrom=fulltext https://doi.org/10.1210/clinem/dgaa865

Provided by Endocrine Society

Earwax Could Be Used to Measure Glucose Levels (Medicine)

An earwax self-sampling device could be used to measure chronic glucose levels, according to a study led by UCL and King’s College London researchers.

©UCL

The pilot study, published in Diagnostics, reports that the new device was almost 60% more reliable at measuring chronic glucose levels averaged over a month than an existing gold standard technique.

Researchers hope that their new method could be an effective, rapid and affordable way to assess glucose levels in people who might have diabetes.

The new device can be used at home without medical supervision, allowing for check-ups while maintaining social distancing, and is easy to use without discomfort.

Lead researcher Dr Andres Herane-Vives (UCL Institute of Cognitive Neuroscience and Institute of Psychiatry, Psychology & Neuroscience, King’s College London) said: “It is estimated globally that one in two adults with Type 2 diabetes are undiagnosed, and the situation is likely to have worsened during COVID-19 as people may not have undergone screening. Many people with Type 2 diabetes already have complications when they are diagnosed, so earlier diagnosis is critical.

“The current gold standard way to test chronic glucose levels requires a blood sample, and is not perfectly reliable as it uses blood proteins as a proxy for the actual sugar levels. We have been working to develop a cheaper, more precise way to measure someone’s long-term glucose levels at any point in time.”

The novel earwax self-sampling device is similar to a cotton swab, but with a brake that stops the swab from going too far into the ear and causing damage. The tip is covered with a sponge of organic material, with a solution that has been tested to be the most effective and reliable at taking samples.

This study, led by researchers in the UK, Chile, Germany and the United Arab Emirates, involved 37 healthy participants who did not have diabetes, whose glucose levels were measured on two days nearly a month apart. The participants’ earwax was sampled using an established clinical method at baseline (first visit) and then using the novel device one month after. At the first visit to the research centre, participants’ blood was sampled after fasting, and at the second visit, their blood was taken after eating a standardised meal.

The blood samples were analysed using standard checks for short-term glucose levels, as well as for glycated haemoglobin (HbA1c), a blood protein that is affected by sugar levels, enabling it to be measured in standard practice to gauge longer-term glucose levels.

The researchers found that the earwax test was almost 60% more effective than glycated haemoglobin tests at reflecting average glycaemia (blood sugar) levels across the whole month, while delivering a result more quickly.

Dr Herane-Vives and colleagues recently published another paper* finding that the device can effectively measure the stress hormone cortisol which may help to monitor depression and stress-linked conditions, and they are also studying if it could test for COVID-19 antibodies that accumulate in earwax.

Dr Herane-Vives is now setting up a company, Trears, to bring his earwax sampling device to market, with support from UCL Innovation & Enterprise at UCL’s entrepreneurship hub for startups at BaseKX, which provides access to a network of experts providing guidance, mentoring and introductions to investors. He and his colleagues are now planning larger trials to test the device, including in people with diabetes.

Diabetes expert and Head of the UCL Centre for Obesity Research, Professor Rachel Batterham (UCL Medicine), who was not involved in the research, commented: “Type 2 diabetes is a leading cause of sight loss, heart attacks, strokes, kidney damange and early death globally. To prevent complications we need to diagnose people as early as possible, yet this has been hampered by lack of an easy-to-use screening test. This new device may allow mass screening and earlier identification of Type 2 diabetes.”

Reference: Herane-Vives, A.; Espinoza, S.; Sandoval, R.; Ortega, L.; Alameda, L.; Young, A.H.; Arnone, D.; Hayes, A.; Benöhr, J. A Novel Earwax Method to Measure Acute and Chronic Glucose Levels. Diagnostics 2020, 10, 1069. https://www.mdpi.com/2075-4418/10/12/1069

Provided by UCL

Better Diabetes Treatment: New Insulin Molecule Can Self-regulate Blood Sugar (Medicine)

Everyday life for the more than 46 million people around the world who suffer from type 1 diabetes could become much easier and safer.

Researchers from the University of Copenhagen and biotech firm Gubra have developed a new insulin molecule that, in the future, will ensure that diabetics receive just the right amount of insulin.

The insulin on the market today is unable to identify whether a patient with type 1 diabetes needs a small or large effect from the insulin, which lowers blood sugar.

“That is why we have developed the first step towards a kind of insulin that can self-adjust according to a patient’s blood sugar level. This has tremendous potential to vastly improve the lives of people with type 1 diabetes,” explains Professor Knud J. Jensen, of the University of Copenhagen’s Department of Chemistry, one of the researchers behind a new study on this new insulin.

Effective in rats

The researchers behind the study developed a type of insulin with a built-in molecular-binding that can sense how much blood sugar is in the body. As blood sugar rises, the molecule becomes more active and releases more insulin. As blood sugar drops, less is released.

“The molecule constantly releases a small amount of insulin, but varies according to need,” says Knud J. Jensen, who continues:

“It will give type 1 diabetes patients a safer and easier treatment. Today, a person with type 1 diabetes must inject themselves with insulin many times throughout the day and frequently monitor their blood sugar level by pricking their finger with a blood glucose meter. This here, allows a person to inject the new insulin molecule less often over the course of a day and thereby think about it less,” says Knud J. Jensen.

Although the new ‘automated’ insulin is a major advance towards better diabetes treatment, it will be a while before the revolutionary insulin becomes a part of diabetics’ everyday lives.

“We’ve tested the insulin molecule on rats and it has proven itself effective. The next step is to develop the molecule so that it works more rapidly and accurately. And finally, to test it in humans—a process that can take many years. But it is certainly worth pinning one’s hopes on,” explains Professor Jensen.

An idea that sprouted in the United States

The idea to create a kind of insulin that self-adjusts to a patient’s needs occurred many years ago, while Professor Jensen was living in the United States. This is where a friend of his with type 1 diabetes recounted to him a story:

“My author friend Jan Sonnergaard told me about a married couple who had been dancing one night. The man had type 1 diabetes and was feeling unwell. The wife thought to stabilize his blood sugar by giving him insulin. Unfortunately, the insulin eventuated in her husband’s death. I wanted to make certain that this kind of tragedy would never be repeated,” says Knud J. Jensen, concluding:

“The difficult thing with diabetes is that insulin always works the same way. It lowers blood sugar, even though that might not be what a patient requires. This is what we seek to address with our new molecule.”

References: Jensen, K..J., Mannerstedt, K., MIshra, N..K., Engholm, E., Lundh, M., Madsen, C..S., Pedersen, P..J., Le-Huu, P., Pedersen, S..L., Buch-Månson, N., Borgström, B., Brimert, T., Fink, L..N., Fosgerau, K. and Vrang, N. (2020), An Aldehyde Responsive, Cleavable Linker for Glucose Responsive Insulins. Chem. Eur. J.. Accepted Author Manuscript. https://doi.org/10.1002/chem.202004878 https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202004878

Provided by University of Copenhagen

Obesity Changes Cell Response to Glucose, Uses Slower Metabolic Path in Mouse Liver (Medicine)

Healthy cells and cells with type 2 diabetes use completely different pathways to manage blood sugar levels, according to results from a study in mice. Researchers used a trans-omic approach, combining data from genes (transcriptomics) and metabolites (metabolomics) to identify and connect the many separate processes involved in responding to glucose.

The trans-omic network includes regulatory pathways that are specific to obese mice and those specific to healthy mice. Color coding highlights pathways that respond to glucose only in normal-weight mice (WT, blue), only obese mice (ob/ob, red), pathways in common (green), and pathways that react in opposite ways in obese and normal-weight mice (pink). Credit: Toshiya Kokaji, CC-BY, first published in Science Signaling, DOI: 10.1126/scisignal.aaz1236

“Many regulatory pathways for diabetes are already well known. What we have done is map the total landscape of diabetes regulation,” said Professor Shinya Kuroda, leader of the Systems Biology Lab at the University of Tokyo. Kuroda’s team previously mapped the different cell signaling pathways activated in response to high or low concentrations of insulin.

“We expected only small differences between the healthy and diabetes regulatory network, but we found they were totally different,” said Kuroda.

Obese mice lack most of the rapid response to glucose found in healthy metabolism, instead relying on much slower methods like changing gene expression.

Building a trans-omic network of glucose response

After eating a meal or sugary drink, insulin triggers cells to allow glucose molecules to move from the blood into cells, where glucose is broken down and converted into energy. In type 2 diabetes, cells become insensitive to insulin, so glucose remains in the blood causing prolonged high blood sugar levels known as hyperglycemia.

Decades of diabetes research have revealed that many signaling pathways become active when glucose is inside the cell. Many of those paths involve enzymes and small molecules called metabolites, which are themselves products of metabolic pathways.

Kuroda’s team studied healthy mice and a strain of mouse with a genetic mutation that causes the mice to overeat and develop diabetes in adulthood. All mice drank sugary water and then researchers waited between 20 minutes to four hours before taking blood samples and dissecting their liver. The liver is a major site of glucose metabolism in both mice and humans.

Researchers used a wide range of experiments to identify molecules that changed in response to glucose.

After collecting the data, researchers searched scientific databases for information about any glucose-responsive molecule they had identified in their measurements. Knowledge in the databases allowed researchers to connect these individual molecules to networks of intercellular signaling pathways.

Trans-omics allows researchers to turn a long list of discrete measurements into a wide web of knowledge about how cells reacted to glucose.

The analysis was complicated by the fact that scientific databases are highly specialized, with different databases dedicated to individual types of molecules. For example, a database about genes is not connected to a database about enzymes.

Project Research Associate Toshiya Kokaji, first author of the research publication, estimates that it took four years to complete the data analysis and construct the trans-omic network.

“Now that the pipeline is defined, we can complete the data analysis and trans-omic network construction in one to two years,” said Kokaji.

Researchers built a five-layered trans-omic map with information about insulin signaling, transcription factors (types of proteins that regulate gene activity), enzymes, metabolic reactions and metabolites.

Mapping cells’ different glucose responses

Color-coding the glucose-responsive molecules that were measured in healthy or obese mice revealed the vastly different signaling paths they use.

Healthy mice rapidly respond to glucose using enzymes and metabolites produced as byproducts of glucose metabolism, returning to normal blood sugar levels in about one hour.

Obese mice lack most of this rapid response, instead changing the expression of some genes over several hours and producing different molecules to cope with the glucose.

This slower and very different approach in obese mice fits the typical understanding of diabetes as the global impairment of metabolic control. Additionally, the approach used in obese mice requires cells to expend more energy compared to the specific and specialized paths activated in healthy cells.

Researchers hope that the data contained in the trans-omic network will allow the research community to find new cell signaling pathways to explore, both generally and for glucose-specific metabolism.

The research team plans to continue their trans-omic analysis of glucose response by adding additional layers of information to the network and studying glucose response in other cell types that consume large amounts of glucose, such as muscle cells.

References: (1) Toshiya Kokaji, Atsushi Hatano, Yuki Ito, Katsuyuki Yugi, Miki Eto, Keigo Morita, Satoshi Ohno, Masashi Fujii, Ken-ichi Hironaka, Riku Egami, Akira Terakawa, Takaho Tsuchiya, Haruka Ozaki, Hiroshi Inoue, Shinsuke Uda, Hiroyuki Kubota, Yutaka Suzuki, Kazutaka Ikeda, Makoto Arita, Masaki Matsumoto, Keiichi I. Nakayama, Akiyoshi Hirayama, Tomoyoshi Soga, Shinya Kuroda, “Trans-omic analysis reveals allosteric and gene regulation-axes for altered glucose-responsive liver metabolism associated with obesity”, Science Signaling, Vol. 13, Issue 660, eaaz1236 2020. DOI: 10.1126/scisignal.aaz1236 https://stke.sciencemag.org/content/13/660/eaaz1236 (2) Kawata K, Hatano A,i Yugi K, Kubota H, Sano T, Fujii M, Tomizawa Y, Kokaji T, Tanaka KY, Uda S, Suzuki Y, Matsumoto M, Nakayama KI, Kaori Saitoh K, Kato K, Ueno A, Ohishi M, Hirayama A, Soga T, and Kuroda S. 11 September 2018. Trans-omic analysis reveals selective responses to induced and basal insulin across signaling, transcriptional, and metabolic networks. iScience. 10.1016/j.isci.2018.07.022

Provided by University of Tokyo

This Protein Is A Key Player In Diabetes, According To Recent Study (Medicine)

According to recent study done by Rina Mostafa and colleagues, a protein called CNOT3, that’s common throughout the body plays a key role in regulating glucose levels. This protein was found to silence a set of genes that would otherwise cause insulin-producing cells to malfunction, which is related to the development of diabetes.

Mice lacking CNOT3 in pancreatic beta cells have fewer insulin-producing cells, leading to diabetes. Credit: OIST

Diabetes is a common disorder that causes very high blood glucose levels. Left untreated, it can lead to serious health problems like kidney failure, heart disease, and vision loss. This disorder occurs when there isn’t enough insulin in the body or when insulin-induced responses are weakened. Insulin normally lets glucose into cells for energy-use and so, without it, glucose builds up in the blood instead. A lack of insulin is often because the pancreatic beta cells, which normally synthesize and secrete insulin, have stopped functioning correctly.

They know that defects in beta cells can lead to high levels of glucose in the blood and, eventually, diabetes. Their results suggested that CNOT3 has a hand in this and plays a key role in maintaining normal beta cell function.

CNOT3 is a jack-of-all-trades. Many organs throughout the body express it, and it regulates different genes in different tissues. But its activity has a common basis—it helps to keep cells alive, healthy, and functioning correctly. It does this through several different mechanisms, such as producing the right proteins or suppressing certain genes.

Here, researchers studied its function in islet cells from pancreatic tissue in mice. These islets are notoriously difficult to work with, taking up just only one to two percent of the pancreas, but they’re where the beta cells are located.

The researchers first looked at whether CNOT3 expression differed in diabetic mice compared with non-diabetic mice. By looking at these islets, they found that there was a significant decrease in the CNOT3 in the diabetic islets as opposed to the non-diabetic ones.

To further investigate the protein’s function, the researchers blocked its production in the beta cells of otherwise normal mice. For four weeks, the animals’ metabolism functioned normally, but by the eighth week, they had developed an intolerance to glucose, and by 12 weeks they had full-blown diabetes.

Without CNOT3, the researchers found that some genes, which are normally switched off in beta cells, switch on and start to produce proteins. Under normal circumstances, these genes are silenced because once they switch on, they cause all kinds of problems for the beta cells, such as stopping them from secreting insulin in response to glucose.

Further research into the cellular mechanisms behind this found a surprising link between CNOT3 and the messenger RNA of these normally switched-off genes. A messenger RNA (mRNA) is a single strand molecule that corresponds to the genetic sequence of a gene and is essential for synthesizing proteins.

Under normal circumstances, the mRNA of these genes hardly expresses. But once CNOT3 was removed, the researchers found that the mRNA was much more stable. In fact, protein was produced from the stabilized mRNA, which have unfavorable effects on normal tissue function. This suggests that at least one way that these genes are kept switch off is through the destabilization of their mRNA, driven by CNOT3.


References: Dina Mostafa et al. Loss of β-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation, Communications Biology (2020). DOI: 10.1038/s42003-020-01201-y link: https://www.nature.com/articles/s42003-020-01201-y