A Sea Snail Toxin Could Inspire New Diabetes Drugs
ABOVE: Fish-hunting cone snails use insulin- and somatostatin-mimicking toxins to induce a state of hypoglycemia in their prey. ©iStock, lilithlita
T hough small, cone snails are formidable hunters, producing a variety of toxins—many of which are valuable for drug research—to immobilize prey and deter predators. In 2015, researchers discovered that some species, like Conus geographus, make venoms that contain con-insulin, a toxin that mimics fish insulin and induces hypoglycemic shock in nearby prey.1
These findings inspired Ho Yan Yeung, a postdoctoral researcher in Helena Safavi-Hemami’s group at the University of Utah, to investigate whether cone snails produced other toxins that mimic fish hormones. While con-insulin quickly lowered blood sugar, Yeung hypothesized that another cone snail version of a glucose-regulating hormone was needed to maintain a longer-lasting effect: keeping blood sugar low to prevent the fish from escaping. One hormone that could serve this function is somatostatin, which acts as a brake to prevent blood sugar from rising to normal levels.
To find these snail-produced hormone mimics, Safavi’s team sequenced RNA from the C. geographus venom gland and used mass spectroscopy to identify two somatostatin-like toxins (Consomatins G1 and G2).2 X-ray crystallography of Consomatin G1 revealed that its structure closely resembled a therapeutic somatostatin analog, prompting further exploration. There are five types of somatostatin receptors (SSTR); human somatostatin binds to all five, while the snail version binds to only one. This research, published in Nature Communications, revealed that C. geographus produced a weaponized somatostatin that exhibits more specific binding to somatostatin receptors than human analogs.3 This discovery could lead to improved targeting for drugs for diabetes.
