Parasite-Killing Drug May Reverse Diabetes By Targeting Fat Cells, Restoring Insulin Sensitivity
Our world's modernization has brought with it a host of health problems, with one of the most prevalent among them being type 2 diabetes. It's only within the past few years that diabetes has manged to grow so drastically, affecting 347 million people worldwide — this number's expected to double in the coming years.
Diabetes medications can only stop symptoms of the disease, and there are currently no treatments for the underlying causes. That's about to change, however, with new research showing that a modified version of the drug niclosamide, which is used to kill intestinal parasites, can also attack diabetes at its source. The research, led by Victor Shengkan Jin from Rutgers University, was published on Sunday in the journal Nature Medicine.
Gastric bypass surgery, a type of weight loss surgery, has been shown to help diabetics control their symptoms, however, it carries a significant risk and can only be performed on very obese patients. So, researchers are trying to find ways to help diabetics for whom weight loss surgery isn't an option. Type 2 diabetes renders the body unable to efficiently use insulin, the hormone that metabolizes blood sugar. In many cases, the pancreas is unable to produce enough insulin, resulting in insulin resistance and rising blood sugar levels.
A major cause of insulin resistance is the accumulation of excess fat in the cells of the liver, as well as in the muscle tissue, Jin said. This fat disrupts the normal functions of insulin, which helps blood sugar energize cells in the tissue. As a result, glucose remains in the bloodstream, damaging tissue and causing blindness, kidney damage, heart disease, and other health problems.
Jin and his colleagues wanted to find a method to eliminate this fat in the liver. Using lab mice and the modified form of niclosamide, called niclosamide ethanolmine salt (NEN), they managed to remove all the excess fat. It "improved the animals' ability to use insulin correctly and reduce blood sugar," Jin said.
NEN burned the excess fat through a process called mitochondrial uncoupling. Mitochondria, the energy factories of the cell, burn fuels like fat and sugar to keep the cells going. "The cell is like a car and the mitochondria are the engine," Jin said in a statement. "What we're doing inside cells is like putting the car's transmission into neutral by uncoupling it from the transmission. Then you step on the gas so the engine runs full throttle but the car doesn't move. If too much of the fuel in the cell is fat, you keep burning it until the fuel gauge reaches empty. Without the interference of fat, you hope that sugar will then enter the cell normally."
Jin theorizes that once the fat from the liver and muscle tissues are cleared, the cells will be able to respond to insulin, enabling them to interact with glucose, and reversing diabetes entirely. While it hasn't been tested on humans yet, the results with mice are encouraging, he said. On top of that, the drug they used was chosen because it's already approved by the Food and Drug Administration.
"We went to the literature and found an approved drug that does in parasitic worms what we wanted to do in liver cells," he said. "The modified form of the medication, although itself is not a drug used in humans, has an excellent safety profile in other mammals. So, very likely, it would have a good safety profile in humans too."
Source: Jin V, et al. Nature Medicine. 2014.