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  • richardmitnick 7:12 am on November 10, 2017 Permalink | Reply
    Tags: A very low calorie diet can rapidly reverse type 2 diabetes in animal models, , PINTA, Type 2 diabetes,   

    From Yale: “Study reveals how a very low calorie diet can reverse type 2 diabetes” 

    Yale University bloc

    Yale University

    November 9, 2017
    Ziba Kashef

    (© stock.adobe.com)

    In a new study, a Yale-led research team uncovers how a very low calorie diet can rapidly reverse type 2 diabetes in animal models. If confirmed in people, the insight provides potential new drug targets for treating this common chronic disease, said the researchers.

    The study is published in Cell Metabolism.

    One in three Americans will develop type 2 diabetes by 2050, according to recent projections by the Center for Disease Control and Prevention. Reports indicate that the disease goes into remission in many patients who undergo bariatric weight-loss surgery, which significantly restricts caloric intake prior to clinically significant weight loss. The Yale-led team’s study focused on understanding the mechanisms by which caloric restriction rapidly reverses type 2 diabetes.

    The research team investigated the effects of a very low calorie diet (VLCD), consisting of one-quarter the normal intake, on a rodent model of type 2 diabetes. Using a novel stable (naturally occurring) isotope approach, which they developed, the researchers tracked and calculated a number of metabolic processes that contribute to the increased glucose production by the liver. The method, known as PINTA, allowed the investigators to perform a comprehensive set of analyses of key metabolic fluxes within the liver that might contribute to insulin resistance and increased rates of glucose production by the liver — two key processes that cause increased blood-sugar concentrations in diabetes.

    Using this approach the researchers pinpointed three major mechanisms responsible for the VLCD’s dramatic effect of rapidly lowering blood glucose concentrations in the diabetic animals. In the liver, the VLCD lowers glucose production by: 1) decreasing the conversion of lactate and amino acids into glucose; 2) decreasing the rate of liver glycogen conversion to glucose; and 3) decreasing fat content, which in turn improves the liver’s response to insulin. These positive effects of the VLCD were observed in just three days.

    “Using this approach to comprehensively interrogate liver carbohydrate and fat metabolism, we showed that it is a combination of three mechanisms that is responsible for the rapid reversal of hyperglycemia following a very low calorie diet,” said senior author Gerald I. Shulman, M.D., the George R. Cowgill Professor of Medicine and Cellular and Molecular Physiology and an investigator at the Howard Hughes Medical Institute.

    The next step for the researchers will be to confirm whether the findings can be replicated in type 2 diabetic patients undergoing either bariatric surgery or consuming very low calorie diets. His team has already begun applying the PINTA methodology in humans.

    “These results, if confirmed in humans, will provide us with novel drug targets to more effectively treat patients with type 2 diabetes,” Shulman said.

    Other study authors are Rachel J. Perry, Liang Peng, Gary W. Cline, Yongliang Wang, Aviva Rabin-Court, Joongyu D. Song, Dongyan Zhang, Xian-Man Zhang, Yuichi Nozaki, Sylvie Dufour, and Kitt Falk Petersen.

    This study was supported by grants from the United States Public Health Service.

    See the full article here .

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    Yale University Campus

    Yale University comprises three major academic components: Yale College (the undergraduate program), the Graduate School of Arts and Sciences, and the professional schools. In addition, Yale encompasses a wide array of centers and programs, libraries, museums, and administrative support offices. Approximately 11,250 students attend Yale.

  • richardmitnick 8:07 am on June 15, 2017 Permalink | Reply
    Tags: , Broccoli, , , Sulforaphane, Type 2 diabetes   

    From COSMOS: “Broccoli may hold key to new diabetes treatment” 

    Cosmos Magazine bloc


    15 June 2017
    Andrew Masterson

    Sulforaphane, a compound found in broccoli, may help in the treatment of type 2 diabetes. Bernard Jaubert

    A chemical compound found in broccoli offers a potential treatment alternative for type 2 diabetes, a study in Science Translational Medicine reveals.

    The compound, sulforaphane, emerged as a possible drug-development target after a team led by Annika Axelsson, of the Lund University Diabetes Centre in Malmö, Sweden, constructed a “disease signature” for type 2 diabetes based on 50 genes and compared the result to “drug signatures” that map interactions between chemicals and their genetic targets.

    Axelsson’s team tested 3,852 compounds and found that sulforaphane – present in many cruciferous vegetables, but especially in broccoli – seemed especially promising.

    In the laboratory the team found that the compound reduced glucose production in cultured human liver cells, and altered liver gene expression in diabetes-affected rats.

    In a follow up trial, Axelsson and colleagues enrolled 97 patients with type 2 diabetes and conducted a 12 week trial, with cohorts given daily concentrated broccoli extract or a placebo control.

    They discovered that the extract “exerts a sustained effect on gene expression”. Obese patients receiving the extract showed significant improvement, they report.

    Sulforaphane has been the focus of much previous research, particularly because of its observed cancer-protective effects, which it achieves by improving the body’s anti-oxidation ability. A March 2017 Japanese study also found it can be used to control obesity. [ https://www.sciencedaily.com/releases/2017/03/170307100402.htm ]

    The compound’s use in managing type 2 diabetes could be of particular appeal for the estimated 15% of patients who cannot take the standard treatment, metformin, because in some cases it can increase the risk of kidney damage.

    However, the scientists caution that the results so far, while encouraging, are still preliminary. Sulforaphane’s clinical deployment, they write, “cannot yet be recommended to patients as a drug treatment but would require further studies, including data on which groups of patients would potentially benefit most from it”.

    See the full article here .

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  • richardmitnick 9:31 am on June 7, 2017 Permalink | Reply
    Tags: , GLP1 (glucagon-like peptide-1), , No more daily insulin shots, , Type 2 diabetes   

    From Science Alert: “This New Treatment Could Provide Weeks of Glucose Control For Type 2 Diabetes Patients” 


    Science Alert

    Syda Productions/Shutterstock

    6 JUNE 2017

    No more daily insulin shots.

    To control their blood sugar levels, people with type 2 diabetes constantly need to rely on medication, but it’s a tricky condition to manage, especially if you need daily insulin shots.

    Researchers have been working on a new method for delivering diabetes drugs to make them last longer in the body. Now a recent study using both mice and monkeys has shown potential for treatments that would only require a couple of injections a month.

    Some of the latest-generation type 2 diabetes drugs contain a molecule called GLP1 (glucagon-like peptide-1), which stimulates insulin production in the body only when it needs more glucose.

    That sounds ideal, but unfortunately, GLP1 has a really short half-life – it breaks down in the body quickly, making it an impractical long-term treatment on its own.

    By combining it with other molecules, it’s possible to extend the half-life of GLP1. But that method still only gets us to about 3-7 days.

    Right now, patients in the US already have some options that can be injected weekly, but scientists are looking for a way to slow down the release of the drug itself.

    Now a team from Duke University has managed to combine GLP1 with a biopolymer molecule that starts out as a liquid in colder temperatures, but thickens into a gel-like substance in reaction to body heat.

    This means the solution can be administered with a simple injection, but once it gets into the body, the drug is released very slowly, so it can control blood glucose levels for longer with just one dose.

    To test how their new solution would work for actual diabetes treatment, the researchers tried the drug in both mice and in rhesus monkeys – two species with well-established diabetes models.

    They got exciting results in both: in mice, the new GLP1 solution controlled glucose levels for 10 days after just one injection; in monkeys, whose metabolism is slower, the effects lasted up to 17 days.

    More than two weeks for one injection is better than any diabetes drug currently on the market.

    The team thinks that because human metabolism is even slower than in monkeys, theoretically the drug could last longer in people, perhaps requiring just one injection a month.

    “Preclinical data presents compelling evidence that this construct would require no more than two injections a month for humans, and possibly as few as one per month, especially given the dose-stacking potential of this system,” the researchers write in the paper.

    The team thinks their new approach to ‘trapping’ GLP1 in the gel-like substance could be applied to other types of medication, too.

    Of course, it’s important to note that so far the method has only worked in animal studies, and scientists will need to do more research to see how the principles would translate to human use.

    GLP1-based medications are currently not the first-line treatment for people with type 2 diabetes, but this sounds like an exciting step towards making diabetes management easier for many.

    The study was published in Nature Biomedical Engineering.

    See the full article here .

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  • richardmitnick 9:05 am on July 28, 2016 Permalink | Reply
    Tags: , , SR10171, Type 2 diabetes   

    From Scripps: “Study Suggests New Drug Candidate Could Treat Both Type 2 Diabetes and Bone Loss” 

    Scripps Research Institute

    July 27, 2016

    In addition to its more obvious ills, type 2 diabetes is a condition closely associated with bone fractures, increasing the risk of fractures twofold. To make matters worse, certain anti-diabetic drugs further increase this risk, particularly in postmenopausal women, severely limiting their treatment options.

    A new study, co-led by Patrick R. Griffin, a professor on the Florida campus of The Scripps Research Institute (TSRI), and B. Lecka-Czernik, a professor at the University of Toledo, has shown that a new class of drug candidates developed at TSRI increases bone mass by expanding bone formation (deposition of new bone) and bone turnover (a normal process of replacement of old bone). A proper balance of these two processes is critical to healthy bone maintanence, and this balance is frequently negatively affected in diabetic patients.

    The result is a new dual-targeting drug candidate—or, as Griffin describes, “one drug addressing multiple therapeutic indications”—that could treat both diabetes and bone disease. The compound has been referenced as “SR10171.”

    The study was published recently online ahead of print by the journal EBioMedicine.

    Diabetes affects more than 29 million people in the United States, according to a 2012 report from the American Diabetes Association. Between 2010 and 2012, the incidence rate was about 1.7 to 1.9 million per year, and in 2013, estimated direct medical costs of the disease were $176 billion.

    Over the past decade, Griffin and his colleague, TSRI Associate Professor Theodore Kamenecka, have focused on the details of molecules that increase sensitivity to insulin (a hormone that regulates blood sugar). Using newly discovered information, the researchers made significant advances in developing a family of drug candidates that target a receptor known as peroxisome proliferator-activated receptors gamma (PPARγ), a key regulator of stem cells controlling bone formation and bone resorption and a master regulator of fat.

    Anti-diabetic drugs known as glitazones (TZDs) target the PPARγ protein, but that interaction leads to severe bone loss and increased fractures. Stem cells in the bone marrow can differentiate either into bone cells or fat cells, and the glitazones drive them to fat at the expense of bone.

    But SR10171 is designed to avoid this troubling outcome. In animal models treated with the compound, fat formation in the bone marrow was successfully blocked independent of their metabolic state (healthy or diabetic).

    “Using structural biology technigues and rational design synthetic chemistry, SR10171 was constructed to engage the PPARγ protein in a unique way possessing an optimal balance with the receptor’s other family member, PPARa, to treat diabetes and, at the same time, improve bone health,” Griffin said. “This targeted polypharmacological approach demonstrates that the target isn’t the problem if you target it correctly.”

    The compound increases bone mass by protecting and increasing the activity of bone cells in various stages of normal bone mantanence, utilizing mechanisms that overlap those that regulate whole-body energy metabolism.

    “SR10171 improves bone mass regardless of body mass index, normal to obese,” Griffin added. “So you could use such a drug to treat osteoporosis whether patients are diabetic or not.”

    The first author of the study, PPARG Post-Translational Modifications Regulate Bone Formation and Bone Resorption, is L.A. Stechschulte of the University of Toledo, Ohio. Other authors include P.J. Czernik, Z.C. Rotter and F.N. Tausif of the University of Toledo; C.A. Corzo, D.P. Marciano, A. Asteian, J. Zheng and T.M. Kamenecka of TSRI; J. B. Bruning of The University of Adelaide, Australia; and C.J. Rosen of the Maine Medical Center Research Institute.

    The study was supported by the National Institutes of Health (grant numbers DK080261 and DK105825); the American Diabetes Association (award 7-13-BS-089), the Abrams Charitable Trust and the Klorfine Family Fellowship.

    See the full article here .

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    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

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