Liver fat may be key to type 2 diabetes

Victor Shengkan Jin says it is important to find a drug for 

type 2 diabetes that attacks the root cause of the disease 

and not just symptoms. – Photo: Nick Romanenko 

Rutgers University

DIABETES DIGEST – Oct. 17, 2014 – Obesity is associated with the rise in type 2 diabetes, but new research suggests that it is not just overall fat that causes insulin resistance, but liver fat.

Dr. Victor Shengkan Jin, an associate professor of pharmacology at Rutgers University Robert Wood Johnson Medical School notes that excess fat in the liver is not just a condition of the obese; people of normal weight can also develop fatty livers and type 2 diabetes.

According to Jin, a major cause of insulin resistance is the accumulation of excess fat in the cells of the liver, as well as in muscle tissue. The fat disrupts the process where, ordinarily, insulin would cause body tissues to correctly absorb blood sugar and use it as a fuel. With nowhere else to go, much of the excess glucose remains in the bloodstream, where in high concentrations it can damage tissues throughout the body.

Based on that observation, Jin and his team looked for an FDA-approved drug that would deplete fat inside liver and muscle cells. They settled on a form of the drug called, niclosamide ethanolamine salt, used for parasitic worms in the intestine. 

"Our goal in this study was to find a safe and practical way of diminishing fat content in the liver. We used mice to perform proof-of-principle experiments in our laboratory," says Jin. "We succeeded in removing fat, and that in turn improved the animals' ability to use insulin correctly and reduce blood sugar."

The study was published in this month’s Nature Medicine. The drug works by a process called mitochondrial uncoupling, whereby the mitochondria, a structure in every cell that normally powers the cell, is tricked into burning excess fat.

"The cell is like a car and the mitochondria are the engine," Jin explains. "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." 

The researchers are hopeful that because they used a drug that has already been FDA-approved that human clinical trials may be approved.

The Centers for Disease Control and Prevention projects that 40 percent of all Americans now alive will develop type 2 diabetes at some time in their lives.