The reduction of the production of insulin has been attributed to kisspeptin 1, which has been noted as a key in the development of diabetes.
A previously unsuspected liver hormone is a key in the development of type 2 diabetes mellitus (T2DM), according to research published in the April issue of Cell Metabolism.
Researchers from Johns Hopkins Medicine studied the hormone kisspeptin 1 (K1) in mice and human blood and liver samples. The hormone was previously known to regulate puberty and fertility, but also slows down the production of insulin, fueling T2DM.
Scientists fattened a group of mice by feeding them calorie-rich food, and the mice predictably developed T2DM. Then, investigators chemically prevented the mice’s livers from making K1, which allowed the insulin levels to return to normal ranges. The mice were able to maintain healthy insulin production and blood sugar levels even while consuming high-fat foods.
Another group of mice were engineered to lack K1 receptors in their pancreases. After eating high-fat foods, those mice maintained healthy levels of insulin and blood sugar.
These two groups of mice led researchers to conclude pancreatic cells’ function is directly suppressed by K1. When the liver is stimulated by high levels of glucagon, K1 is released in the blood stream, which suppresses insulin secretion on the pancreatic beta cells.
“Our findings suggest that glucagon issues the command, but K1 carries out the orders, and in doing, so it appears to be the very cause of the declining insulin secretion seen in T2DM,” lead investigator Mehboob Hussain, MD, said in a press release. “Glucagon and insulin alone never really made complete sense. There was always something missing and, we feel, K1 is a very good candidate to be that missing part. All our findings point in this direction.”
Similarly, researchers found increased K1 levels in blood and liver samples from human patients with T2DM.
The researchers theorize that the identification of K1 as a key regulator in T2DM will lead to new drug initiatives. Instead of injecting synthetic insulin to maintain blood sugar levels, restoring natural insulin production could cure T2DM.
Next, researchers plan to study the hormone-like substance they believe blocks K1 receptors in mice to test it in human pancreas cell samples. If the mice receptor-blocker can restore the function of human pancreas cells, it would add credibility to the idea that diabetes is a common disease across species.
“Sugar provides critical fuel when an animal enters combat or is trying to run away from a predator,” Hussain says. “The high levels of insulin after a meal can cause dangerously low levels of blood sugar, which would render the animal weak and vulnerable. So our theory is that K1 is a defense mechanism that halts the sugar-reducing effects of insulin in such life-and-death situations.”