Top Stories - Diabetes & Obesity

New TRI Facility in Downtown Orlando
Translational Research...

Florida Hospital and Sanford-Burnham announce the opening of the Florida Hospital –...

Bernie Machen
University of Florida...

University of Florida President Bernie Machen has joined the Sanford-Burnham Board of Trustees and...

Dr. Daniel Kelly, scientific director at Sanford-Burnham’s Lake Nona campus in Orlando, Fla. and senior author of the study
Super athletic mice burn more...

Dr. Daniel Kelly and colleagues show that generating energy from sugar leads to fitter muscles and...

Personalized Medicine Partnership of Florida
Introducing the Partnership...

Sanford-Burnham, Moffitt Cancer Center, and Florida Hospital will collaborate to create a...

Drug discovery case study: high-throughput screening of TNAP

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Editor’s note: this is the second in a series of posts highlighting drug screening studies in our Conrad Prebys Center for Chemical Genomics. Read the first post here.

Calcification of the medial layer of arteries is increasingly recognized as an important clinical problem. Medial vascular calcification (MVC) is the major cause of morbidity and mortality in generalized arterial calcification of infancy (GACI), and contributes to cardiovascular deterioration in Kawasaki disease (KD), chronic kidney disease (CKD), as well as in diabetes, obesity, and aging. MVC is thought to result from decreased circulating levels of the mineralization inhibitor, inorganic pyrophosphate (PPi).

Researchers at Sanford-Burnham have revealed that the development of MVC in mouse and rat models is accompanied by up-regulation of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme whose primary function is to hydrolyze PPi, and thus, crucial in determining where mineralization occurs. Preliminary data have proven that upregulation of TNAP is sufficient to cause MVC and Sanford-Burnham scientists have developed potent drug-like inhibitors of TNAP.

Presidential advisor John P. Holdren visits Sanford-Burnham at Lake Nona

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We’re always thrilled to have public officials visit our facilities in California and Florida, but last Friday was an especially exciting day for scientists and staff at Sanford-Burnham’s Lake Nona campus in Orlando, Fla. Dr. John P. Holdren, advisor to President Barack Obama, toured Orlando’s Medical City and spent time at the Sanford-Burnham site to learn about the promising research that is being conducted in our Diabetes and Obesity Research Center.

Dr. Holdren is assistant to President Obama for science and technology, director of the White House Office of Science and Technology Policy (OSTP), and co-chair of the President’s Council of Advisors on Science and Technology (PCAST). Congress established the OSTP in 1976 to advise the President and others within the Executive Office of the President on the effects of science and technology on domestic and international affairs. The OSTP also makes recommendations on the annual NIH budget.

A “twisted” grand opening ceremony

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“My goal is to cure diabetes,” Steven Smith, M.D., scientific director of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes (TRI), said boldly at the opening ceremony of the TRI’s new state-of-the-art facility in downtown Orlando on March 27. “We believe that personalized medicine is our best shot at discovering cures for our most serious health problems like diabetes.”

The ceremony’s highlight was the unveiling of a spectacular nine-foot double-helix DNA structure that will be placed at the main entrance of the building, symbolizing the fundamental research being conducted at the TRI, as well as the synergies and collaborations the TRI represents. Selected board members and presenters each added one illuminated “bar,” representing a nucleotide, to the double helix.

“This is one of those rare times when the reality far exceeds the dream,” said John Reed, M.D., Ph.D., CEO of Sanford-Burnham. “The TRI is a wonderful opportunity for our organization, which will bring more and more to life our slogan From Research, the Power to Cure. We’re very excited about this opportunity to take our relationship with Florida Hospital to the next level.”

Translational Research Institute establishes new research paradigm for metabolic diseases

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Florida Hospital and Sanford-Burnham today celebrate the opening of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes’ (TRI) new state-of-the-art facility in downtown Orlando, Fla., dedicated to the advancement of a new paradigm of personalized approaches to researching and treating diabetes and obesity.

“We are witnessing the rise of personalized medicine, most notably in cancer. Our goal at the TRI is to accelerate the advancement of personalized medicine in diabetes and obesity,” said Steven Smith, M.D., Sanford-Burnham professor and scientific director of the TRI.  “We are working to rapidly expand knowledge of complex genetic and molecular causes of diabetes and obesity so that we can better define disease subpopulations. By working independently and in partnership with industry, we hope to develop therapies and treatment approaches tailored to those subpopulations. Our ultimate goal is that our discoveries will someday lead to cures for certain patients.”

Obesity research advances to clinical testing

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Discoveries made in the laboratories of Sanford-Burnham will, for the first time, advance to the clinical research stage involving human studies at the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes (TRI). The research will focus on orexin, an appetite-inducing hormone produced in the brain, which appears to resolve obesity without requiring a reduction in food consumption or elevation in physical activity. This research exemplifies the translational research focus at Sanford-Burnham and the TRI – advancing science from laboratory bench to patient bedside. The studies will provide insight into individual responses and contribute to the development of personalized therapies for treating metabolic diseases – a focus area for both the TRI and Sanford-Burnham.

Appetite-suppressing drugs have traditionally been the basis of weight-loss treatments since obesity is thought to be caused by excessive energy intake and low physical activity. However, appetite suppressants can produce unacceptable side effects and, after the treatment ends, patients usually the weight they lost. Recent data indicate that orexin leads to weight loss by releasing excess energy as heat instead of storing it.

University of Florida president joins Sanford-Burnham Board of Trustees

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We are very proud to announce that University of Florida (UF) President Bernie Machen, D.D.S., Ph.D., has joined Sanford-Burnham’s Board of Trustees. He will be the fourth Floridian to serve on our board. Current Florida-based trustees include Allen R. Weiss, former president of Walt Disney Parks and Resorts, and James E. Jardon II, chief executive officer of JHT, Incorporated.

“As president of one of Florida’s leading research universities, I am honored to join Sanford-Burnham’s Board of Trustees,” said Machen. “My relationship with Sanford-Burnham dates back to 2006, when the Institute first considered opening a new campus in Orlando. Over the years we’ve developed strategies that will benefit our individual and shared scientific endeavors. I look forward to my role on the board and the many new partnership opportunities to come.”

Taking stock: obesity research progress with Takeda

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Scientists from the Diabetes and Obesity Research Center and their colleagues from Florida Hospital recently returned from Japan, where they reviewed the progress that has been made at the mid-point of a research partnership with Takeda Pharmaceutical. The two-year collaboration focuses on the discovery and evaluation of new therapeutic approaches to obesity. In Japan, Sanford-Burnham scientists reported benchmark data that sets the stage for a key element in future drug development—the testing of obesity drug candidates.

“The data generated thus far lays the groundwork for analysis of how individuals respond differently to disease,” said Steven R. Smith, M.D., director of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes (TRI), where the clinical studies are being performed with volunteers. “This partnership with Takeda, TRI, and Sanford-Burnham establishes a model to accelerate the development of safe and effective therapies.”

Introducing the Partnership for Personalized Medicine in Florida

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Sanford-Burnham, Moffitt Cancer Center, and Florida Hospital announced today that they will collaborate to create a Personalized Medicine Partnership of Florida (PMP Florida). The partnership will conduct research to speed up discovery and develop new treatments in the areas of cancer and metabolic diseases, including obesity, diabetes,  and cardiovascular disease.

The organizations will utilize new molecular and genomic technologies to discover, translate, and personalize interventions for preventing and treating diseases more efficiently to improve outcomes, while reducing costs. The partnership will speed up the discovery and development of new treatments by bringing together the complementary strengths of Florida Hospital’s large patient population and clinical research expertise; Sanford-Burnham’s fundamental research expertise and technology platforms; and Moffitt’s biospecimen bank (samples of tissue, cells, blood, etc.), data warehouse, and personalized medicine capabilities.

Tasting fructose with the pancreas

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Taste receptors on the tongue help us distinguish between safe food and food that’s spoiled or toxic. But taste receptors are now being found in other organs, too. In a study published online February 6 by the Proceedings of the National Academy of Sciences, Sanford-Burnham researchers discovered that beta cells in the pancreas use taste receptors to sense fructose, a type of sugar. According to the study, the beta cells respond to fructose by secreting insulin, a hormone that regulates the body’s response to dietary sugar.

“Before this study, fructose’s effect on insulin release was not appreciated. Fructose, and especially high-fructose corn syrup, is found in everything from sodas to cereals, but it remains to be seen whether dietary fructose is good or bad for beta cells and human metabolism,” said Björn Tyrberg, Ph.D., adjunct assistant professor in the Diabetes and Obesity Research Center at Sanford-Burnham’s Lake Nona campus in Orlando and senior author of the study.

Heart hormone helps shape fat metabolism

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It’s well known that exercising reduces body weight because it draws on fat stores that muscle can burn as fuel. But a new study at Sanford-Burnham suggests that the heart also plays a role in breaking down fat. In their study, published February 6 in the Journal of Clinical Investigation, Sheila Collins, Ph.D. and colleagues detail how hormones released by the heart stimulate fat cell metabolism. These hormones turn on a molecular mechanism similar to what’s activated when the body is exposed to cold and burns fat to generate heat. This study adds another dimension to our understanding of how the body regulates fat tissue and may someday lead to new ways to manipulate the process with drugs to reduce weight in obese patients or maintain it in individuals who experience pathological weight loss during chronic heart failure.

“Exercise is always going to raise your blood pressure some, so there’s the potential that these heart hormones—called cardiac natriuretic peptides—are being released and contributing to the breakdown of fats,” said Collins, professor in the Diabetes and Obesity Research Center at Sanford-Burnham’s Lake Nona campus in Orlando and senior author of the study. “Over a period of time, natriuretic peptides could also be leading to an increase in the numbers of brown fat cells, which we know are very important for protection against diet-induced obesity, at least in laboratory experiments.”

How antipsychotics cause side effects such as obesity and diabetes

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In 2008, roughly 14.3 million Americans were taking antipsychotics—typically prescribed for bipolar disorder, schizophrenia, or a number of other behavioral disorders—making them among the most prescribed drugs in the U.S. Almost all of these medications are known to cause metabolic side effects such as obesity and diabetes, leaving patients with a difficult choice between improving their mental health and damaging their physical health. In a paper published January 31 in the journal Molecular Psychiatry, researchers reveal how antipsychotic drugs interfere with normal metabolism by activating a protein called SMAD3, an important part of the transforming growth factor beta (TGFβ) pathway.

The TGFβ pathway is a cellular mechanism that regulates many biological processes, including cell growth, inflammation, and insulin signaling. In this study, all antipsychotics that cause metabolic side effects activated SMAD3, while antipsychotics free from these side effects did not. What’s more, SMAD3 activation by antipsychotics was completely independent from their neurological effects, raising the possibility that antipsychotics could be designed that retain beneficial therapeutic effects in the brain, but lack the negative metabolic side effects.

Sanford-Burnham experts talk about why Americans are fat

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New Year’s resolutions and dieting seem to go hand-in-hand. Setting a personal goal to lose weight and exercise more may jump-start the New Year but “February frustration” can derail even the most determined. Scientists in Sanford-Burnham’s Diabetes and Obesity Research Center recently shared their expertise on the causes of weight gain and the metabolic challenges that make it so hard to keep off the extra pounds. Their insights on genetics, diet, metabolism and lifestyle were included in a four-part series called “What’s making Americans so fat?” that ran in the Orlando Sentinel beginning January 1. Medical reporter Marni Jameson spoke with national obesity experts to compile a list of 40 reasons for why 60 percent of U.S. adults are obese or overweight.

“It’s not gluttony, and it’s not lack of willpower,” says Dr. Steven Smith, scientific director of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes. “No scientist in the field will say the problem is strictly one of willpower,” he says. “It’s a result of the way our genes are interacting with an environment that is stacked against them.”

Here’s an excerpt of how the experts weighed in:

All weight gain is not the same

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Malnutrition in its many forms remains a world-wide epidemic. In the United States, more than 60 percent of adults are classified as overweight or obese, whereas third-world nations are struggling with under-nutrition and insufficient food supplies. A new study provides scientific insight that may benefit development of public health policy to influence healthy weight gain.

The study, published January 4 in the Journal of the American Medical Association (JAMA), examines the impact of diets containing varying amounts of protein on weight gain, body composition, and energy expenditure. The research, led by Sanford-Burnham’s Steven R. Smith, M.D. and George Bray, M.D., Pennington Biomedical Research Center, found that total calories account for increases in body fat, while increasing the percent of dietary protein during overfeeding led to more lean body mass storage. This work appears to be the first to analyze the impact of dietary protein during overfeeding and provides guidance on dietary composition for healthy weight gain.

How a few extra mice prompted a diabetes collaboration

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Dr. Barbara Ranscht and her lab are working to better understand how T-cadherin—a protein found on the surface of neurons, muscle, and other cells—regulates communication between cells during development and disease. The best way to go about this is to see what happens when the protein is missing. To do this, her lab developed a mouse model that lacks the protein altogether. Using these animals, Dr. Ranscht’s group has revealed that T-cadherin protects the stressed heart and is necessary for new blood vessel growth in injury models.

One day, Dr. Ranscht found herself discussing possible roles for T-cadherin in metabolism with Sanford-Burnham colleagues Dr. Björn Tyrberg and Dr. Fred Levine. The researchers especially wondered about T-cadherin’s role in the pancreas (Drs. Tyrberg’s and Levine’s organ of expertise).

Super athletic mice burn more sugar

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Muscle performance and fitness are partly determined by how well your muscle cells use sugar as a fuel source. In turn, exercising improves the muscle’s ability to take up sugars from the bloodstream and burn them for energy. On the flip side, conditions that reduce physical activity—such as obesity or chronic disease—reduce the muscle’s capacity to burn sugar. Sanford-Burnham scientists are now unraveling a mechanism that re-programs metabolic genes in muscles in a way that increases their capacity to use sugar. When activated in mice, this metabolic re-programming dramatically improves exercise performance.

These findings, published December 1 in Genes & Development, reveal new targets that could be explored to increase the ability of muscles to burn sugars—an avenue that could ultimately lead to new prevention or treatment methods for obesity, metabolic syndrome, and diabetes.