A team of American researchers may have identified a drug that can do it all – reversing diabetes and obesity all while helping us build stronger bones.
Common diabetes treatments often leave patients prone to bone fractures and osteoporosis. This is because many diabetes medications often have a negative side effect: they block our body’s natural ability to produce new bone. The World Health Organization (WHO) estimates that over 415 million people across the world are living with diabetes, many of which suffer from increased risks of bone fractures and osteoporosis.
At the Scripps Research Institute, Dr. Anutosh Chakraborty and his team of molecular biologists have been studying a strain of mutant mice resistant to diabetes and obesity. They found that the animals were missing a gene that produced the enzyme, Inositol Hexakisphosphate Kinase 1 (IP6K1). This enzyme is a key component involved in signaling mesenchymal stem cells – a type of stem cell in the bone marrow – to mature into either fat cells or bone cells. When we consume a high-fat diet, the enzyme becomes overactive, leading to the overproduction of fat cells in place of bone cells. But because these mice were missing the gene entirely, no matter how much fat they ate, they could never overproduce the fat cells.
When colleagues Dr. Siddaraju Boregowda and Dr. Donald Phinney had heard of their discovery, it prompted them to ask: well what about their bones? If the stem cells weren’t becoming fat cells, were they becoming bone cells instead?
To observe if diabetes and obesity-resistant mice were now also resistant to bone deterioration, the researchers fed them either a regular diet or a high-fat diet for a period of eight weeks. To their surprise, not only were the bone cells in the mutant mice not being replaced by fat cells, the mutant mice ended up producing more bone cells than regular mice.
The team then set out to see if they could reproduce that effect using the drug, TNP (2,4,6 – trinitrophenol or better known as picric acid). TNP is commonly used by researchers as an inhibitor of the IP6K1 enzyme and is currently under investigation as a possible diabetes medication. When the scientists repeated the experiments on regular mice, this time supplementing their high-fat diet with periodic injections of either TNP or a placebo, they found that the mice treated with TNP had more bone cells, fewer fat cells, and stronger bones overall. This cutting-edge discovery was recently reported in Science.
At this point, the researchers are still figuring out how to selectively deliver the drug to mesenchymal stem cells, but they are captivated by the potential TNP could play in preventing bone loss in patients with diabetes and obesity. Boregowda says they may even start exploring how TNP could repair and heal broken bones in other diseases. Phinney, on the other hand, is aiming for the stars. He’s interested how the drug might prevent bone deterioration in astronauts working in zero-gravity. In either case, fractures might soon be a thing of the past.
Written by Calvin J. Chan B. Sc.
Yasinski, E. (2017, September 5). New therapy could protect diabetic bones. Science Magazine. Retrieved from http://www.sciencemag.org/news/2017/09/new-therapy-could-protect-diabetic-bones.