EPAC2 may be the key to curing type II diabetes

The next time you contemplate the glazed munchy selection at the FFC, do your pancreas a favor and think of this article. Consistently combating fatigue with sugary pick-me-ups can seriously burn out your beta cells, which can only lead to one thing: diabetes.

Diabetes is a condition that affects millions of Americans each year. The disease contributes to cardiovascular problems and forces patients to adhere to a restricted lifestyle. Scientists estimate that approximately 26 million Americans are afflicted with diabetes, the majority of whom suffer from type II diabetes.

Type II and type I diabetes are commonly confused. Type I diabetes is the result of genetics and those who suffer from the condition cannot produce insulin. On the other hand, type II diabetics suffer from insulin resistance and are therefore unable to control blood sugar level. However, recently, researchers at Hopkins Children’s Center discovered an important protein that could alleviate the effects of type II diabetes, potentially treating millions of Americans.

A research team led by Mehboob Hussain, a pediatric endocrinologist at Hopkins Children’s Center, found that the protein EPAC2 is more important than what previous studies had shown. The team determined that EPAC2 is a vital regulator in insulin production. The protein stimulates insulin-producing cells in the pancreas when more insulin is needed. The cells then respond by producing more sugar-regulating hormone.

In diabetics, this process is somewhat disrupted. Type II diabetics suffer from the dysfunction of certain cells known as beta cells. These beta cells are pancreatic cells responsible for secreting insulin, the hormone needed to maintain blood sugar level. When insulin is released, glucose in the blood stream is transported to tissues and organs as either energy sources or storage in the form of fat cells. The releasing process of insulin is called exocytosis. When people develop type II diabetes, the beta cells are too fatigued to produce the necessary amount of insulin. Type II diabetics develop this condition through chronic overeating. Every time the body ingests food, extra insulin is released. As people overeat over a long period of time, the beta cells have to work longer and harder to maintain the necessary blood sugar level. As a result of overworking, the beta cells will slowly lose their capability to produce insulin. With the cessation of insulin production, glucose builds up in the bloodstream resulting in type II diabetes.

Researchers are curious about the signaling protein EPAC2 and its role in the regulation of insulin production. Hussein explains how past experiments on the role of EPAC2 had been done in cell cultures, however researchers were yet unaware on how EPAC2 would work on the entire organism. As a result, the research team at Hopkins sought to study the effect of EPAC2 in organisms. In experiments involving mice, the researchers first investigated the effects of EPAC2 in healthy mice. First, healthy and lean mice were given a regular diet. Researchers then measured their blood sugar levels and found that the mice, even without EPAC2 to signal insulin production, managed to regulate their blood sugar, maintaining it at a safe level. However, when researchers gave the mice a high-fat, month-long diet, the mice without EPAC2 developed conditions similar to those of type II diabetics. These experiments suggest that EPAC2 plays an important role in regulating high sugar levels produced by overeating.

To further study the mechanism under which EPAC2 works, researchers put cells with and without EPAC2 under the microscope. Scientists discovered that cells with EPAC2 are able to regulate the amount of calcium inside the cell while the cells without EPAC2 cannot perform the same functions. The amount of calcium inside the cell is important since calcium is a catalyst that signals the cell to release insulin. Hussein describes how EPAC2 seems to be involved in regulating the rise of calcium in the cell before exocytosis occurs.

Despite the clear role of EPAC2 demonstrated in insulin production and release, scientists still cannot tell whether diabetes results from a lack of EPAC2 or vice versa. Since type II diabetics were healthy at first, it demonstrates that the patients originally have adequate amounts of EPAC2.

However, scientists cannot determine whether overeating depletes the ability of EPAC2 to stimulate insulin-producing cells or if chronic high sugar levels from overeating damage the EPAC2 protein, compromising its ability to regulate insulin.

While the relationship remains unclear, researchers remain optimistic about diabetes treatment. They believe drugs that target the EPAC2 protein will still help stimulate the beta cells and maybe even cure diabetes.