The race is on to find effective treatments for diabetes and obesity, both of which are nearing epidemic levels worldwide. Now, new findings published in Proceedings of the National Academy of Sciences show that a specific peptide, ShK-186, selectively blocks the activity of a protein that promotes inflammation through Kv1.3, one of the body’s potassium channels. By blocking inflammation, the peptide can combat the harmful effects of obesity and insulin resistance.
ShK—a peptide derived from sea anemone venom—was discovered in the 1990s by a research team at the University of California, Irvine, led by George Chandy, M.D., a professor of physiology and biophysics. Chandy's team found that Shk blocked the Kv1.3 channel very effectively.
"This is a new twist in a sustained journey of discovery for people who suffer from the potentially lethal consequences of metabolic syndrome and autoimmune diseases," Chandy said in a press release. Chandy and his UC Irvine colleague Michael Calahan have been studying sea anemone venom and its effect on Kv1.3 since 1984.
In their current study, obese mice were fed a high-fat, high-sugar diet. Treatment with Shk-186 was found to reduce weight gain, the buildup of white fat cells, fatty liver disease, blood cholesterol levels, and blood sugar levels in the mice.
Shk-186 works by activating calorie-burning brown fat, while suppressing white fat and improving liver function.
In 2009, UC Irvine licensed ShK-186 to Kineta Inc., a Seattle-based biotechnology company. Kineta is currently conducting clinical trials of ShK-186 to treat autoimmune inflammatory diseases, such as multiple sclerosis, psoriatic arthritis, and lupus. The company has also been given license to test ShK-186 to treat metabolic syndrome and obesity.
Fighting Diabetes by Combating Obesity
Several new diabetes drugs have been developed in the past 20 years, but despite these strides, the incidence of type 2 diabetes continues to grow.
Ping H. Wang, MD, co-author of the study and chief of endocrinology at the UC Irvine Diabetes Center, told Healthline that ShK-186 is different from diabetes treatments now on the market.
“Obesity contributes to the development of type 2 diabetes. ShK-186 is different because it also helps control diabetes by improving obesity,” Wang explained. “ShK-186 works by improving blood glucose...and glucose tolerance by enhancing insulin sensitivity. The drug increases the uptake of glucose by calorie-burning brown fat.”
In the future, ShK-186 may be used as the basis for new therapeutic strategies, alone or in combination with other medications, to treat diabetes and its related metabolic disorders.
Gary V. Desir, M.D., is a Yale medical professor and an expert on the Kv1.3 channel's role in glucose metabolism. “While additional studies are needed, the potential clinical relevance of this work is enormous,” Desir said in a press release. “No Kv1.3 inhibitor, as a drug candidate for obesity, has reached the clinic until now.”
According to the World Health Organization, the obesity rate has nearly doubled worldwide since 1980. In 2008, more than 200 million men and nearly 300 million women, worldwide, were obese.
Given the food industry’s tendency to produce high-fat, high-sugar foods, finding an effective treatment for obesity and type 2 diabetes can’t come too soon.