Julio Ayala Archives - Sanford Burnham Prebys
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Exciting diabetes and obesity research highlights from Medical City

AuthorDeborah Robison
Date

May 22, 2017

Center for Metabolic Origins of Disease

With more than one-third of adults in the U.S. considered obese, scientists are searching for new ways to treat obesity and associated health problems such as type 2 diabetes. Four researchers from Sanford Burnham Prebys Medical Discovery Institute (SBP) at Lake Nona have been invited to present new perspectives and insights at the American Diabetes Association’s 77th Scientific Sessions, to be held June 9-13, 2017, in San Diego. The conference is the world’s largest gathering of research experts and clinicians focused on diabetes research, prevention and care. The presentations will inform new treatment strategies for the nearly 30 million people diagnosed with diabetes.

Potential early therapeutic target for diabetes prevention
Obesity often leads to accumulation of fat in muscle and faulty machinery involved in taking up glucose from a meal to use it for energy, leading to type 2 diabetes. A recent advance from the laboratory of Daniel P. Kelly, MD, scientific director of SBP at Lake Nona, may lead to a way to stop this pre-diabetic state from advancing. Dr. Kelly will present findings on a recently discovered cellular glucose sensor in muscle that serves as a key connection between insulin resistance and accumulation of fat in muscle, which occurs in obesity-related diabetes. When the protein is inhibited in skeletal muscle cells, regulatory genes that influence glucose uptake and insulin signaling are enhanced. The team is now validating the pathway as a therapeutic target to prevent type 2 diabetes.

Fatty liver and type 2 diabetes
Peter Crawford, MD, PhD, director of SBP’s Cardiovascular Metabolism Program, is studying the root causes of nonalcoholic fatty liver disease (NAFLD), a condition that affects nearly 80 percent of people with type 2 diabetes. About 5 percent of NAFLD cases advance to liver cirrhosis – a disease characterized by scarring and fibrosis that could require liver transplant. Dr. Crawford is an expert on how the liver processes energy derived from food. At the ADA meeting, he will discuss how the interruption of normal fat metabolism can lead to enhanced scarring. Through ongoing research, he hopes to be able to specifically identify which diabetes patients are at risk of developing advanced liver disease and to develop therapies that protect against disease progression.

Brain nutrient sensors help maintain energy balance
Diabetes researcher Julio Ayala, PhD wants to understand how specialized regions in the brain control food intake, energy expenditure and body weight. His ADA presentation will focus on how nutrient-sensors that control the balance between energy-consuming and energy-producing processes in almost every cell in our bodies also play a very specific role in the brain. His research shows that hormones, such as glucagon-like peptide-1 (GLP-1) regulate the activities of these brain nutrient sensors to influence hunger, satiety and ultimately body weight. Defective sensors are implicated in obesity and could be a target for new therapeutic treatments.

Glucose Sensor in Macrophages
Insulin resistance is a key feature of type 2 diabetes. When present, the impairment prevents insulin from getting glucose into muscle where it’s used for energy, and instead causes blood sugars to become elevated. The events that drive the development and progression of insulin resistance are not known. Laszlo Nagy, MD, PhD, director of SBP’s Genomic Control of Metabolism Program, will present new research that suggests that the inflammatory process—and specifically a type of white blood cells called macrophages—are involved. He will present a novel hypothesis on the role of macrophages, defined in Greek as “big eaters”, and identify molecules involved in muscle growth and glucose metabolism. His research aims to reveal cellular interactions that could become new therapeutic targets to treat type 2 diabetes.

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SBP scientists reflect on progress in diabetes research

AuthorDeborah Robison
Date

June 23, 2016

“The most significant advances in diabetes treatment, which were underscored at the ADA meeting, is the clinical evidence that two newer classes of anti-diabetic drugs significantly improve cardiovascular outcomes and overall mortality. These drug families are insulin secretion enhancers such as liraglutide (LEADER trial) and drugs that promote glucose elimination in the urine, such as canagliflozin and empagliflozin (EMPA-REG OUTCOME trial). This has major impact because reducing the risk of heart disease is always the end goal in treating diabetes—the association with heart disease is what makes type 2 diabetes so serious. These trials also present a remarkable opportunity for basic researchers—many of us, including several here in Lake Nona, study how drugs in these classes affect metabolism. The answers to those questions should lead to new drug targets that are even more specific and precision-oriented.”

Peter Crawford, MD, PhD
Associate Professor and Director
Cardiovascular Metabolism Program

“From the sessions that I saw, there was a significant emphasis on combination treatments—either combining two or more already approved drugs that have related functions or generating fusions of multiple protein drugs. An example of the former is the combination of basal insulin and glucagon-like peptide-1 receptor agonists to control fasting and post-meal glucose levels, respectively. With regards to fusion proteins, there were many posters and presentations highlighting efforts to generate dual and triple combinations that would lower glucose and aid weight loss. These approaches may reduce the need for patients to take multiple drugs and therefore improve efficacy and patient adherence.”

Julio Ayala, PhD
Associate Professor
Integrative Metabolism Program
ADA Thomas R. Lee Career Development Award Recipient ’14

“During the ADA meeting two symposia and numerous other presentations examined evidence implicating gut microbiota in the development of type 1 and type 2 diabetes. I am personally enthusiastic about the potential of novel therapeutic strategies that either prevent harmful changes in gut microbiota or even directly transplant “therapeutic” microbial species. Nevertheless, our current understanding of the potential mechanisms is very limited due to the complex factors affecting the microbiome such as the host’s genetics and the environment (diet, antibiotic use, history of infections etc.).”

George Kyriazis, PhD
Assistant Professor
Integrative Metabolism Program

“Of particular interest to me were the symposia on experimental strategies for understanding how the brain controls metabolism. Specifically, optogenetics and magnetogenetics are emerging as two powerful research tools for this purpose, and involve genetically modifying neurons to express either light- or magnetic field-sensitive proteins so that their activity can be controlled with fiber optic light or magnets, respectively. These sophisticated techniques will help investigators delineate which regions in the brain play a critical role in regulating blood glucose, which could lead to more effective therapies for diabetes and obesity.”

Melissa Burmeister, PhD
Staff Scientist
Dr. Julio Ayala Lab

 

Institute News

SBP scientists join race for a cure

Authordrobison
Date

March 17, 2016

Andrew Carley, PhD, has a personal motivation for finding a cure for diabetes. As one of the 29 million Americans with diabetes, he became a biomedical researcher to better understand the causes of disease.

For Julio Ayala, PhD, a passion for medical research was sparked by his grandmother, a type 1 diabetic, who at age 86 has successfully managed the disease most of her life.

Julio Ayala, PhD
Julio Ayala, PhD

Siobhan Malany, PhD, is an avid cyclist who believes so strongly in team efforts that she has enlisted robots to join her research team searching for new drugs to fight disease.

On Sunday, March 13, 2016, these Sanford Burnham Prebys scientists took their interest in biomedical research to the roadways of Central Florida as they joined 1,100 participants in the 2016 Tour de Cure at Lake Nona bicycle ride for diabetes. The twelve-member SBP team collectively pedaled more than 400 miles and raised $9,000 to fight the disease. Participants began the 25, 63, and 100-mile courses in Lake Nona Medical City near SBP and the Center for Metabolic Origins of Disease, the site where researchers study diabetes in hopes of identifying new, more effective therapies.

“It was a fun way to give back and do what I love to do.  Cycling has been my commute, my sport and my escape —now it’s a way to contribute,” said Malany, who completed the 100-mile course in five hours. She enjoyed the camaraderie and credited the group with a bit of competitive motivation. “I kept a 21.5 mile per hour pace, which was not something I would have accomplished had I been cycling alone. It was fast and fun being in a pack because you conserve energy by drafting,” added Malany.

Siobhan Malany, PhD
Siobhan Malany, PhD

Since moving to Lake Nona in December from Chicago, Carley has gotten back into cycling and now bikes to the Institute in Medical City each day. He completed a Century ride to mark the 20th anniversary of the Tour de Cure in 2011 in Chicago and decided to mark the 25th anniversary of the event with a 25 mile ride. “I selected the 25 mile course because it was the maximum length of time my 3-year old daughter would remain content in her bike stroller watching a Toy Story movie. She weighs only 32 pounds and the course was relatively flat so we were able to complete the ride in two hours despite frequent stops,” said Carley.

Tour-de-cure

Team captain Ayala participated in various ADA and JDRF fund raising events while at Vanderbilt University. “While riding my bike to work a few years ago, I saw the first Tour de Cure in Lake Nona and knew that I wanted to participate. We study diseases of metabolism at the Medical City site and a number of faculty, including me, receive ADA-funded grants, so I wanted to get involved,” said Ayala.

Ayala credits the team’s spirit with providing extra motivation to push through the extreme winds encountered on the course. It’s with similar determination that they approach their daily race for the cure in their research labs.

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The Diabetes Story: Will new treatments lead to novel weight loss drugs?

AuthorGuest Blogger
Date

November 3, 2015

Written by Jing Ping Lu, PhD

November is American Diabetes Month. Throughout the month, we will be highlighting our research contributions to this increasingly prevalent disease.

The growing epidemic of diabetes presents significant challenges for health care. It ranks 7th among the leading causes of death, and about one tenth of all health care dollars are spent on diabetes and its complications. According to the American Diabetes Association, 29.1 million Americans have been diagnosed with this metabolic disorder, and 1.4 million new cases were reported in 2013. With these statistics, the burden diabetes has on the health care system will continue to rise.

Opportunities to research the disease have also increased with the growing diabetic population. One particular area of emphasis is in understanding how glucose—a type of sugar—is broken down, or metabolized, in diabetic patients. Glucose is the major energy source our body uses to carry out activities. Glucose levels in the blood are kept constant by a hormone called insulin. After eating, the glucose level in the blood rises and signals insulin release. Insulin is like a key that opens up the locks on our cells so that glucose can enter. Glucose can then be stored in the form of glycogen and used later for energy. If our body does not make enough insulin, or insulin is not well recognized by the cell, then glucose levels will build up in the blood stream causing diabetes and other long-term complications.

Treating Diabetes Diabetic treatments are primarily developed to lower the amount of blood glucose by restoring the secretion of insulin or enhancing how well insulin works to promote the entry of glucose into cells. Another hormone called glucagon-like-peptide-1(GLP-1) has been shown to increase glucose-dependent stimulation of insulin release, and GLP-1 based drugs are used to treat diabetes. Julio Ayala, PhD, and his research team are working on projects that utilize GLP-1 based drugs to stimulate insulin secretion. These drugs come in two categories, GLP-1 analogs that mimic the action of GLP-1 and dipeptidyl peptidase 4 (DPP-4) inhibitors that prevent the breakdown of GLP-1 made in the body. Although both drugs can effectively lower glucose levels, one promotes weight loss while the other does not.

A new avenue for weight loss? Preliminary research performed in Ayala’s lab confirmed that the two drugs have different effects on food intake. “Interestingly, when targeted to specific regions in the brain, GLP-1 analogs reduce food intake to a greater degree than does native (natural) GLP-1. This may partly explain why GLP-1 analogs promote weight loss while DPP-4 inhibitors that increase native GLP-1 levels do not,” Ayala explained. “This leads us to speculate that even though both drugs bind to the same receptor in the feeding centers of the brain, they activate different molecular mechanisms in cells of the brain and this eventually results in different effects on food intake, and therefore, weight loss.”

As Ayala’s team continues to explore the mechanism of action, they hope to identify the critical steps that lead to the reduction in food intake. “Obesity is a leading risk factor for developing Type 2 diabetes. If we can discover the steps that GLP-1 analogs engage to promote weight loss, then drugs can be designed to specifically target these steps. This would provide a new avenue for designing drugs to treat obesity,” Ayala added, “and that could deliver a greater benefit to diabetes patients and contribute to decreasing the rise in Type 2 diabetes. We are excited to see the possibilities.”

Dr. Julio Ayala is an assistant professor at Sanford Burnham Prebys Medical Discovery Research Institute in Lake Nona, Fla and a recipient of an American Diabetes Association research award.

This post was written by Jing Ping Lu, PhD, a post-doctoral associate in Dr. Rastinejad’s lab in Lake Nona.

Institute News

A summer of learning and research

Authoradmin
Date

August 20, 2014

All around Central Florida, students are returning to school for the fall semester. At Sanford-Burnham in Lake Nona, we take a closer look at some of the lab experiences of our high-school interns who have spent part of their summer in our labs getting a taste for what it’s like to work in basic-science research.

Continue reading “A summer of learning and research”