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Absence of exendin-4 effects on postprandial glucose and lipids in the Gila monster, Heloderma suspectum

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Abstract

Circulating nutrients serve as energy resources for functioning tissues throughout the body. While the tight regulation of plasma nutrients has been extensively studied in mammals, investigations into specific metabolic regulators in reptiles have been limited and have revealed conflicting results. The peptide exendin-4, which was isolated from the saliva of Gila monsters, Heloderma suspectum, has demonstrated prolonged plasma glucose-lowering properties in mammals. Although exendin-4 has often been labeled a venom protein, circulating plasma levels of exendin-4 have been shown to increase in response to feeding. Because exendin-4 has glucose-regulating effects in mammals, we hypothesized that post-prandial elevation in circulating exendin-4 levels in Gila monsters reduces plasma glucose and triglycerides. To examine the effect of exendin-4 on circulating nutrients, we measured plasma glucose, triglyceride, and cholesterol levels of Gila monsters in response to one of four treatments: fed live mice (a natural post-prandial increase in exendin-4), force-fed dead mice while anesthetized (no post-prandial exendin-4 increase), force-fed dead mice while anesthetized and injected with exendin-4 immediately after feeding (exogenous increase in exendin-4), and force-fed dead mice while anesthetized and injected with exendin-4 24 h after feeding (delayed exogenous increase in exendin-4). After prey ingestion, glucose and triglyceride levels increased significantly over time in all treatment groups, but there was no significant treatment effect. Plasma exendin-4 levels showed significant time and treatment effects, but did not correspond to glucose and triglyceride levels. Our results demonstrate that plasma nutrient levels in Gila monsters respond relatively slowly to feeding and that exendin-4 does not have the same effect on circulating glucose in Gila monsters as it does in mammals. Further studies are necessary to determine whether circulating exendin-4 has an alternate role in regulating other components of energy metabolism such as nutrient uptake rate in the small intestine.

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Acknowledgments

We would like to thank Garet Heintz and Pam Smith at Amylin Pharmaceuticals who processed the plasma samples and thus made this study possible. This research was funded by the School of Life Sciences at Arizona State University and was conducted under Arizona State University’s Institutional Animal Care and Use Committee protocol #05–794R as required legally by the USA.

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Authors and Affiliations

  1. School of Life Sciences, Arizona State University, Tempe, AZ, 85287-4601, USA

    Carolyn M. Christel & Dale F. DeNardo

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  1. Carolyn M. Christel
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  2. Dale F. DeNardo
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Correspondence to Carolyn M. Christel.

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Communicated by H.V. Carey.

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Christel, C.M., DeNardo, D.F. Absence of exendin-4 effects on postprandial glucose and lipids in the Gila monster, Heloderma suspectum . J Comp Physiol B 177, 129–134 (2007). https://doi.org/10.1007/s00360-006-0115-6

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  • DOI: https://doi.org/10.1007/s00360-006-0115-6

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