Scientists are one step closer to a new drug which could reduce blood sugar levels in people with insulin resistance. What’s more, the drug could come without any side effects.
Insulin resistance raises the risk of developing type 2 diabetes. In this condition, cells can no longer respond to the commands from the hormone insulin, which is responsible for regulating blood glucose.
So, restoring the insulin sensitivity could be an efficient method for treating and preventing diabetes. However, current insulin-sensitizing drugs increase the lipid production which can cause wide range of side effects, including weight gain.
Scientists from the Columbia University Diabetes Center in New York City conducted a study which shows a possibility of improving insulin sensitivity without causing weight gain. The study was published in the online journal Cell.
Previous efforts to find a way to improve insulin resistance without causing accumulation of fat were unsuccessful.
Current insulin resistance medications might cause weight gain as they target and block FOXO1. However, while inhibiting, this protein lowers the production of glucose in the liver. So, besides lowering blood sugar levels, it also boosts the production of fat, or lipids.
Dr. Accili reports that using a broadly acting protein FOXO1 inhibitor in the treatment of insulin resistance can cause different adverse effects, like weight gain. So, alongside getting the good from FOXO1 insulin sensitizers, you are also getting the bad.
That’s why scientists have been looking for ways to block this protein without affecting the production of lipids.
Dr. Accili’s team of researchers started their study with mice experiments. They wanted to understand the exact way in which FOXO1 controls the production of glucose in the liver. Also, to discover how is that different from the way FOXO1 regulates the production of lipids.
What they discovered is that in order to restrict the production of lipids, the protein teams up with SIN3A – a transcriptional regulatory protein.
So, this means that if the researchers discover molecules that act on the FOXO1 ability to regulate the glucose production without influencing SIN3A, it could reduce blood sugar and improve insulin sensitivity without increasing lipids or fat.
Scientists screened over million tiny molecules for the next phase of their research. They identified plenty of tiny molecules which could inhibit the protein FOXO1 and lower the production of glucose in liver cells while avoiding SIN3A.
In other words, this means reducing the glucose production in the liver without increasing the accumulation of triglycerides. Even though the research offers proof of concept only, researchers think their discovery could help the development of new treatments for insulin resistance.
Overall, the researchers are excited by the possibility of developing a safer treatment for diabetes. Their next step is to optimize the molecules for animal experiments and provide the basis for clinical trials.