Type 2 diabetes, the most common form of the disease, is a chronic condition that reduces the body’s ability to process glucose (blood sugar). It commonly occurs in people who are obese. While Type 1 diabetes (the kind believed to be linked to genetics) is relatively rare, Type 2 diabetes affects almost 10 percent of the U.S. population (29.1 million people). Another 40 percent (86 million adults) have prediabetes, or higher than normal blood sugar levels, according to the U.S. Centers for Disease Control and Prevention.
Researchers in UCLA’s Metabolic Research Theme are working to find ways that metabolism can unlock the key to preventing or curing Type 2 diabetes. Two avenues of exploration hint that changing the way the pancreas secretes insulin might keep people healthy.
Researchers have long thought Type 2 diabetes occurs because tissues resist the effects of insulin or because the pancreas doesn’t make enough insulin to sufficiently regulate blood sugar. Either way, the result is too much insulin secreted into the blood, leading to insulin resistance.
“Diabetes usually starts when too much insulin is secreted into the blood, leading to insulin resistance. We argue that the way to treat diabetes is to make the beta cell secrete less insulin.”
- Dr. Orian Shirihai
Normally, the hormone insulin, produced by beta cells in the pancreas, regulates the movement of blood sugar into cells. The cells burn or store the sugar. In Type 2 diabetes, this process doesn’t function as it should.
Too much blood sugar is indeed linked to obesity, which is a strong risk factor for Type 2 diabetes. But Orian Shirihai, MD, PhD, director of the Metabolic Theme, believes the disease actually stems from poor quality control in mitochondria within pancreatic beta cells. Read more about mitochondrial quality control.
Dr. Shirihai and his team argue that:
Many obese people develop Type 2 diabetes, requiring long-term treatment with insulin or other medications. Marc Liesa-Roig, PhD, an assistant professor in the department of medicine, aims to better understand the metabolism of people with obesity who don’t develop Type 2 diabetes.
The ability to avoid Type 2 diabetes may come down to hemes (iron-containing molecules). Heme is an essential component of mitochondrial function, because it helps with the electron transport chain that produces usable energy in the form of ATP (adenosine triphosphate). The best-known heme is hemoglobin, which transports oxygen in the blood.
“Our goal is to discover how to alter ROS signaling so that pancreatic beta cell mitochondria can adapt to obesity and secrete as much insulin as needed, eliminating need for therapy. That requires, we believe, modulating ROS levels, perhaps by manipulating heme.”
- Dr. Marc Liesa
Liesa-Roig is working to understand the paradox of heme, obesity and Type 2 diabetes: