Emma Heart studies the role of energy metabolism in Type 2 diabetes [multimedia]

Despite advances in drug therapies for diabetes, maintaining optimal blood sugar (glucose) levels has remained a challenge for health care practitioners and patients.

USF Health’s Emma Heart, PhD, studies how glucose communicates with the metabolic machinery of pancreatic beta cells to release appropriate amounts of insulin and how this process is altered in Type 2 diabetes, the most common form of diabetes.  But her laboratory’s research also takes into account that glucose regulation likely involves an intricate interplay of many other hormones in addition to insulin, which affect multiple target tissues such as the pancreas, liver, muscle and fat.

Emma Heart PhD

Emma Heart PhD, of the Department of Molecular Pharmacology and Physiology, is an expert in islet physiology, in particular pancreatic beta cell metabolism. 

COPH sound-icon-png   Listen to Dr. Heart talk about why she joined USF Health.

“We need a holistic approach to understand how this hormonal matrix influences metabolism in order to attain the ultimate goal of preventing or more effectively treating diabetes, a metabolic disease,” said Dr. Heart, an associate professor in the Department of Molecular Pharmacology and Physiology.

Dr. Heart’s laboratory also looks at how three other hormones fit into the mix with insulin  — glucagon, which raises the concentration of glucose in the bloodstream; leptin, which helps regulate energy balance by inhibiting hunger; and adiponectin, secreted by fat cells to help regulate the metabolism of lipids and glucose.

Blood glucose levels begin to rise after eating as digestion breaks down carbohydrates into sugar molecules, including glucose. Pancreatic beta cells respond quickly, secreting some of their stored insulin into the bloodstream where the hormone enables glucose to enter cells in the body, particularly muscle and liver cells.

Emma Heart PhD

Dr. Heart lifts vials out of a liquid nitrogen tank in the tissue culture laboratory.

Type 2 diabetes develops when the body does not respond properly to insulin. At first the pancreas produces extra insulin to compensate for this insulin resistance, but over time the pancreas cannot make enough insulin. With too little insulin, the body can no longer move glucose from the blood into the cells, causing blood glucose levels to increase.

“Normally, glucose is maintained in such a narrow range that even a little bit more can become a problem,” Dr. Heart said. “When glucose accumulates in the blood, eventually complications from elevated levels can damage the heart, kidneys, nerves or eyes.”

Emma Heart PhD

The liquid nitrogen tank, which Dr. Heart refers to as a “cell hotel,” stores a variety of pancreatic beta, liver, muscle and fat cells — all targets of hormones affecting metabolism.

Dr. Heart came to USF Health in 2015 from the Cellular Dynamics Program, Marine Biological Laboratory in Woods Hole, MA.  For the last few years she and long-term collaborator Joshua Gray, PhD, a toxicologist at the U.S. Coast Guard Academy, have focused on plasma membrane electron transport, or PMET, an ancient system first characterized in plants that transports electrons out of the cell.  However, this system operates in all cell types, and they discovered that it is critical for pancreatic beta cell function.

They received a five-year, $1.8-million R01 grant from the National Institute of Diabetes and Digestive and Kidney Diseases to define the underlying mechanism and consequences of PMET in glucose metabolism, insulin secretion and the overall health of pancreatic beta cells. Dr. Heart, working closely with Dr. Gray, is also the principal investigator of a $337,000 American Diabetes Association grant investigating the role of the xenobiotic enzyme NQO1 for metabolic control in pancreatic beta cells and its effect on insulin secretion.

“Emma is an expert in islet physiology, in particular beta cell metabolism,” said Dr. Gray, who spends summers working with Dr. Heart in her laboratory.  “We have had a very productive ongoing collaboration investigating the response of beta cells to toxicants, including redox cycling chemicals, carcinogens and oxidative stress.”

Gray_Joshua_RSS

Joshua Gray, PhD, a toxicologist at the U.S. Coast Guard Academy in New London, CT, is a long-time collaborator with Dr. Heart, investigating the response of pancreatic beta cells to environmental toxicants. – Photo provided by J. Gray

Dr. Heart and colleagues study how environmental toxicants — plasticizers such as BPA and flame retardants like polybrominated diphenyl ethers — may change metabolic balance and insulin secretion. Preliminary experiments have shown that adding very low doses of flame retardants to test media containing pancreatic beta cells stimulates the cells to secrete more insulin.

“Having too much insulin in the body can be as bad as having too little, because hyperinsulinemia can contribute to the development of obesity, insulin resistance, and eventually lead to diabetes,” Dr. Heart said. “The Goldilocks principle – not too much, not too little, just the right amount of insulin — definitely applies when it comes to the metabolic balance needed to convert glucose into energy for cell use.”

While seeking to better understand what causes energy metabolism to go awry and promote Type 2 diabetes, Dr. Heart is also looking for natural compounds to help alleviate the symptoms of diabetes without the side effects of drugs.

She has identified plant-derived quinones that may help normalize metabolism and promote pancreatic beta cell health, including a quinone (thymoquinone) found in the seeds of the spice black cumin.

COPH sound-icon-png Dr. Heart comments on her research goals.

 

Emma Heart PhD

Dr. Heart, here with laboratory manager Xiaomei Liang, is testing plant-derived quinones to evaluate if the natural compounds can alleviate diabetes symptoms without the side effects of drugs.

Pancreatic beta cells chronically exposed to elevated glucose convert excess glucose into fat, which is detrimental to beta cell function, Dr. Heart said. “In the laboratory, when we apply very low levels of this quinone compound to pancreatic beta cells this conversion to fat is attenuated. The beta cells burn more glucose rather than store it as fat.”

She is currently comparing fat composition, gene expression and other metabolic factors in three groups of mice – those eating a normal diet, those fed a high-caloric diet that promotes weight gain and higher than normal blood glucose levels (hyperglycemia), and those fed the same fattening diet to which the black cumin quinone has been added. More study is needed, but preliminary results indicate that the mice fed the high-caloric diet plus the quinone compound are gaining less weight and have lower fasting blood glucose levels than the mice consuming only a high-caloric diet, Dr. Heart said.

This mouse-model study will examine quinone action on other metabolic tissues besides pancreatic beta cells, including fat and liver.  Huquan Yin, PhD, a postdoctoral fellow and liver metabolism expert who recently joined Dr. Heart’s laboratory, will assist with the project.

Emma Heart PhD

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A native of the Czech Republic, Dr. Heart received her PhD in physiology and biophysics from the University of Southern California and completed an NIH-supported postdoctoral fellowship at Boston University, focusing on metabolism and insulin secretion. During her decade as a research scientist at MBL in Woods Hole, MA, she held faculty appointments at the University of Maryland and the University of Rhode Island.

Something you may not know about Dr. Heart:  She loves animals and volunteered for many years at a cat shelter in Falmouth, MA. After her 21-year-old cat Meow passed away, she adopted a 5-year-old black cat that she named Dracek, or “little dragon” in Czech.

Emma Heart PhD

Test tubes containing extracts from insulin-secreting cells are spun to prepare samples for analysis.

Photos by Eric Younghans, USF Health Communications and Marketing