Release of exendin-4 is controlled by mechanical action in Gila monsters, Heloderma suspectum

Exendin-4 is a peptide produced exclusively by the salivary glands of the Gila Monster, Heloderma suspectum. Although exendin-4 is considered a venom component, circulating plasma levels of exendin-4 have been shown to increase in response to feeding. Previous studies using mammals have demonstrated exendin-4 has prolonged plasma glucose-lowering properties. While these findings suggest a possible role of exendin-4 as a metabolic hormone in the Gila Monster, the mechanism controlling its release by the salivary gland has not previously been studied. We investigated possible factors driving exendin-4 release by testing Gila Monsters' response to one of six treatment groups: fed egg, fed juvenile rat, gastric intubation with egg while under anesthesia, olfactory stimulation from egg without ingestion, unfed control, and biting without feeding. These treatments were designed to separately test actions associated with feeding and different food types. We measured plasma exendin-4 levels using an immunoenzymetric assay before and at three time points after each treatment. Exendin-4 levels increased significantly in groups where considerable biting occurred but not in the other treatment groups. These results suggest that exendin-4 is released from the salivary glands in response to mechanical stimulation and not the detection of food either by smell, taste, or distention of the gut. Further study of exendin-4 in its natural organism is needed to elucidate the functional role of exendin-4 as a venom component and/or a metabolic regulator.