Roughly one fifth of older Americans suffer from adult-onset diabetes. This form of the disease, also known as type 2 diabetes, arises when insulin-producing cells in the pancreas fail to make enough of the hormone, or cells in the body become resistant to its influence, causing blood sugar levels to rise. This surge, in turn, can lead to potentially life threatening effects. The Western medicine chest currently holds no cure for type 2 diabetes, though treatments can preserve and prolong life. But taking a cue from traditional Chinese medicine, researchers have uncovered a specific chemical from the fruit of the gardenia plant that seems to attack the root of the disease.
Researchers Bradford Lowell of Harvard Medical School, Chen-Yu Zhang of Nanjing University and their team set out to find a compound that would block the activity of an enzyme known as uncoupling protein 2 (UCP2). This protein helps a cell's mitochondria convert food molecules into energy, but also inhibits pancreas cells from secreting insulin. It appears in high concentrations in both animal and human diabetics. "We think the increase in UCP2 activity is an important component of the pathogenesis of diabetes," Lowell explains. "Our goal therefore was to discover a UCP2 inhibitor."
Zhang suggested probing the fruit of Gardenia jasminoides Ellis based on its use in Chinese medicine. Pancreas cells from mice treated with the extract released insulin whereas those from mice genetically modified to lack UCP2 showed no change, suggesting the extract worked by blocking that protein. "When I first saw the results, I was in disbelief," Lowell recalls.
Subsequent analyses isolated the responsible molecule: genipin, previously known for its ability to bind proteins. By adding it to mouse pancreatic tissue in vitro, the researchers restored the cells' sensitivity to blood glucose levels and reduced insulin levels. A version of genipin altered to remove its binding abilities showed similar--though weaker--effects. That is important for any subsequent therapies because genipin's protein-linking abilities could lead to a host of side effects, Lowell says. The research appears in the current issue of Cell Metabolism.