J Comp Physiol B (2007) 177:129–134 DOI 10.1007/s00360-006-0115-6 123 ORIGINAL PAPER Absence of exendin-4 eVects on postprandial glucose and lipids in the Gila monster, Heloderma suspectum Carolyn M. Christel · Dale F. DeNardo Received: 7 June 2006 / Revised: 4 August 2006 / Accepted: 9 August 2006 / Published online: 14 September 2006  Springer-Verlag 2006 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 speciWc metabolic regulators in reptiles have been lim- ited and have revealed conXicting results. The peptide exendin-4, which was isolated from the saliva of Gila monsters, Heloderma suspectum, has demonstrated prolonged plasma glucose-lowering properties in mam- mals. 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 eVects in mammals, we hypothesized that post-prandial eleva- tion in circulating exendin-4 levels in Gila monsters reduces plasma glucose and triglycerides. To examine the eVect of exendin-4 on circulating nutrients, we measured plasma glucose, triglyceride, and cholesterol levels of Gila monsters in response to one of four treat- ments: 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 exen- din-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 signiWcantly over time in all treatment groups, but there was no sig- niWcant treatment eVect. Plasma exendin-4 levels showed signiWcant time and treatment eVects, 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 eVect on circulating glucose in Gila monsters as it does in mammals. Fur- ther studies are necessary to determine whether circu- lating exendin-4 has an alternate role in regulating other components of energy metabolism such as nutri- ent uptake rate in the small intestine. Keywords Exendin-4 · Glucose · Triglyceride · Heloderma suspectum · Nutrient regulation Introduction Regulation of circulating nutrients is critical to assure adequate energy resources for functioning tissues throughout the body. In mammals, plasma glucose levels are carefully regulated by a counter-balancing of the glucose-raising eVects of glucagon and the glucose- lowering eVects of insulin (Schreibman et al. 1993). These two hormones are also important in the regu- lation of lipid processing and plasma triglycerides (Schreibman et al. 1993). In reptiles, the regulation of circulating nutrients by insulin and glucagon is much less clear. Reptiles are of particular interest not only because they represent an ancestral system but also because energy resource regulation is likely under diVerent selective pressures due to their much lower metabolic rate. Communicated by H.V. Carey. C. M. Christel (&) · D. F. DeNardo School of Life Sciences, Arizona State University, Tempe, AZ 85287-4601, USA e-mail: carolyn.christel@asu.edu