The Gila Monster (Heloderma suspectum) is one of only two lizard species believed to be venomous. This lizard produces a peptide, exendin-4,exclusively in the salivary glands, that is thought to be used for prey capture or defense. However, a recent study where the Gila Monster's natural prey and predators were injected with exendin-4 found that the protein did not impair the victims at all. Another recent study found that plasma levels of exendin-4 in Gila Monsters increased dramatically following feeding. Thus,rather than being a venom component, exendin-4 may have a physiological role in digestion and absorption-related events. Carolyn Christel and Dale DeNardo of Arizona State University were interested in investigating what this role was, and since no one had previously studied this interesting problem, the team decided to start at the very beginning. They wanted to know the mechanism controlling the protein's release during feeding.
They surmised that the postprandial elevation in circulating exendin-4 levels could result from secretory stimuli associated with prey detection,prey capture and/or prey digestion/absorption. However, given that exendin-4 originates in the salivary glands, the team hypothesized that mechanical events associated with prey capture (i.e. biting and chewing) would provide the greatest stimulus for exendin-4 release. To test their hypothesis, the team measured Gila Monster plasma exendin-4 levels before and at 15 min, 45 min and 24 h following one of six treatments designed to test the effects of different feeding actions and food types on exendin-4 release. The treatments consisted of: (1) lizards fed gelatinous egg mixture, (2) lizards fed intact juvenile rat, (3) gastric intubation of anaesthetised lizards with gelatinous egg, (4) stimulation of unfed lizards with egg scent, (5) unfed lizards, and(6) lizards that bit, but were not fed.
The team found that plasma exendin-4 levels increased significantly in lizards that did a lot of biting, but not in other treatment groups. In the Gila Monsters that were fed juvenile rat or stimulated to bite without eating,plasma exendin-4 levels were significantly higher at the 15 min and 45 min measurement times, but by the 24th hour, the exendin-4 levels had returned to control levels. Christel and DeNardo argue that these results suggest that exendin-4 is released from salivary glands in response to mechanical stimulation (i.e. chewing movements) and not the detection of food by smell,taste or gut distention.
Just how exendin-4 enters the blood of the Gila Monster once released from the salivary glands remains a mystery. This is an intriguing question because salivary glands are not known to have an endocrine function in vertebrates,and proteins in general have limited ability to cross cell membranes. Likewise, the physiological consequences of elevated plasma exendin-4 in the Gila Monster remain to be discovered. However, Christel and DeNardo expect that exendin-4 has an important role in digestion and food absorption following a meal. The team explains that when injected into mammalian species,exendin-4 results in a prolonged decrease of plasma glucose levels - a phenomenon that makes exendin-4 attractive as a potential therapeutic treatment in diabetes. Since Gila Monsters are binge feeders that consume very large meals at infrequent intervals, Christel and DeNardo predict that exendin-4 plays an important role in the metabolism of foods that require lengthy pre- or post-absorption processing.
