American Diabetes Association 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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Is there a type 3 diabetes?

AuthorGuest Blogger
Date

November 10, 2015

This article was written by guest blogger Jessica Frisch-Daiello, PhD

People with type 2 diabetes are twice as likely to develop Alzheimer’s disease—a type of dementia affecting behavior, memory, and cognitive functions. According to the Centers for Disease Control and Prevention, in 2013 Alzheimer’s ranked sixth and diabetes was seventh as the leading causes of death in the United States. Recent studies are suggesting a link between insulin resistance in the brain and Alzheimer’s disease, prompting some researchers to consider a new classification for the disease: type 3 diabetes.

People with diabetes can’t effectively break down blood sugar. Either their bodies don’t produce enough insulin (type 1 diabetes) or their bodies become desensitized to insulin (type 2 diabetes).

The exact mechanisms between insulin resistance and Alzheimer’s disease are not well understood and research is on-going. However, studies suggest that insulin resistance in the brain leads to the formation of two pathological hallmarks of Alzheimer’s disease—the formation of tau tangles and the build-up of clusters of beta amyloid peptides called plaques in the brain. The degree of insulin resistance is correlated with the amount of plaques deposited between nerve cells. Plaques create a blockade that inhibits cell-to-cell signaling in the brain. Additionally, insulin dysfunction has also been shown to affect the formation of tau tangles by mediating the activity of an important enzyme in the body, GSK-3β (glycogen synthase kinase 3).

Juan Pablo Palavicini, PhD, an SBP postdoctoral fellow in the lab of Xianlin Han, PhD, is studying the role of a particular class of molecules found in the body that might give more clues to the mechanisms connecting these two seemingly disparate diseases. According to Palavicini, “We have found that a specific lipid class called sulfatide is severely deficient in the brains of both Alzheimer’s disease patients and type 2 diabetics. Moreover, our research shows that when sulfatide is removed, there is a dramatic change in insulin levels, beta amyloid peptides, and tau tangles. We are currently exploring therapeutic techniques to restore sulfatide content as a treatment for both diseases.”

Sulfatide serves many functions in the body, including aiding neural plasticity and memory. It also plays a role in insulin secretion. A change in the expression of sulfatide has been associated with a number of conditions, including Alzheimer’s disease, Parkinson’s disease, and diabetes.

Given the association between Alzheimer’s disease and diabetes, it is important for people to incorporate healthy habits in everyday life. Both the American Diabetes Association and the Alzheimer’s Association say that daily exercise, social interaction, and a diet emphasizing fruits, vegetables, and whole grains may reduce the risk of developing, or slowing the progression of, these diseases.

Dr. Palavicini and Dr. Han are pursuing this research as part of a mentor-based postdoctoral fellowship awarded by the American Diabetes Association. This article was written by Dr. Jessica Frisch-Daiello, a postdoctoral associate in Dr. Han’s laboratory at SBP.

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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.

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Genes promote hardening of arteries in type 2 diabetes

Authorsgammon
Date

July 15, 2014

Type 2 diabetes has become a national epidemic, affecting nearly 26 million children and adults in the U.S. and approximately 170 million worldwide. According to the American Diabetes Association, $245 billion in costs are associated with diabetes, and 1 in 5 health-care dollars is spent caring for diabetics. A significant portion of the health costs associated with diabetes are those attributed to complications of the disease—including heart attacks, heart failure, stroke, dementia, chronic kidney disease, and amputations of the lower limbs. These complications emerge partly from hardening of the arteries caused by calcium deposits—a process known as arterial calcification—and are much more common in type 2 diabetics than in non-diabetics. Continue reading “Genes promote hardening of arteries in type 2 diabetes”