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For animals exhibiting range residency, the home range is a useful framework to quantify space use. Some reptiles can live decades in the wild and experience extreme environmental variation that influences patterns of habitat use. Individuals may modify their use of space over time, reducing the utility of single‐year home range estimates. Very high frequency (VHF) telemetry data were collected for Gila monsters (Heloderma suspectum) at three Mojave Desert sites in Clark County, Nevada, and home range utilization distributions were calculated using an autocorrelated kernel density estimator. Home range size was consistent within individuals and populations, and home range size did not vary across years at any site. To measure home range fidelity (year‐to‐year reuse), we calculated Bhattacharyya's coefficient (BC) for each combination of years in which an individual was tracked and averaged estimates across individuals and populations. The average BC score was 0.86 (scale from 0 to 1; 0 = no overlap and 1 = complete overlap) and did not vary among populations. We modeled home range area accumulation to estimate the minimum sample size needed for asymptotic stability and found home range accumulation to be dynamic and variable within and across years and individuals. Analysis of the frequency of movement by individuals, average distance traveled per movement, and cumulative distance traveled per active season revealed that movement patterns vary considerably by year. Heterogeneity of space use among populations and individuals suggests that individual and local environmental variation, rather than annual variation in resource availability, may drive home range size and movement patterns of Gila monsters in southern Nevada. Annual variability in movement patterns did not translate to variability in home range size or location, and the species exhibits extremely high philopatry, using the same areas for periods of at least 3–5 years. [ABSTRACT FROM AUTHOR]

We describe the histological appearance of the osteoderms (ODs) of Heloderma suspectum and Varanus komodoensis using multiple staining and microscopy techniques to yield information about their morphology and development. Histological analysis showed that the ODs of H. suspectum are composed of three main tissue types, a superficial layer, herein identified as osteodermine, capping a base composed of Sharpey‐fibre bone and lamellar bone rich in secondary osteons (Haversian bone tissue). In contrast, ODs in V. komodoensis are composed of a core of woven bone surrounded by parallel‐fibred bone without a capping tissue. Thus, in these two species, ODs differ both in terms of their structural composition and in details of their skeletogenesis. The histology of the mineralised tissues observed in these two reptile taxa provides insights into the mechanism of formation of lizard ODs and presents a direct comparison of the histological properties between the ODs of the two species. These data allow greater understanding of the comparative histological appearance of the dermal bones of lizards and highlight their structural diversity. [ABSTRACT FROM AUTHOR]

Type II diabetes mellitus (T2DM) is a chronic non‐communicable disease due to abnormal insulin actions causing uncontrolled hyperglycaemia. The treatment for T2DM, for instance, metformin and incretin mimetic, mainly focuses on the restoration of insulin sensitivity and secretion. Exendin‐4 is a short incretin‐mimetic peptide consisting of 39 amino acids. It is discovered in the venom of Heloderma suspectum as a full agonist for the glucagon‐like peptide 1 (GLP‐1) receptor and produces insulinotropic effects. It is more resistant to enzymatic degradation by dipeptidyl‐peptidase‐4 and has a longer half‐life than the endogenous GLP‐1; thus, it is further developed as an incretin hormone analogue used to treat T2DM. The helical region of the peptide first interacts with the extracellular N‐terminal domain (NTD) of GLP‐1 receptor while the C‐terminal extension containing the tryptophan cage further enhances its binding affinity. After binding to the NTD of the receptor, it may cause the receptor to switch from its auto‐inhibited state of the receptor to its auto‐activated state. Exendin‐4 enhances the physiological functions of β‐cells and the up‐regulation of GLP‐1 receptors, thus reducing the plasma glucose levels. Moreover, exendin‐4 has also been found to ameliorate neuropathy, nephropathy and ventricular remodelling. The therapeutic effects of exendin‐4 have also been extrapolated into several clinical trials. Although exendin‐4 has a reasonable subcutaneous bioavailability, its half‐life is rather short. Therefore, several modifications have been undertaken to improve its pharmacokinetics and insulinotropic potency. This review focuses on the pharmacology of exendin‐4 and the structure‐function relationships of exendin‐4 with GLP‐1 receptor. The review also highlights some challenges and future directions in the improvement of exendin‐4 as an anti‐diabetic drug. [ABSTRACT FROM AUTHOR]

Role of exendin-4 in the Gila monster: Further lessons regarding human oral glucagon-like peptide-1 therapy? Although it is not altogether unusual for regulatory peptides to be found at low concentrations in the saliva of humans, the large amount of exendin-4 in Gila monster saliva is unlikely to have evolved by chance and must have some functional purpose. However, as an alternative and to test bioactivity, we administered exendin-4 orally, together with glucose, to fasted non-diabetic mice and compared the insulin-releasing and glycaemic responses to those induced by glucose given alone or with GLP-1 (Figure 1). [Extracted from the article]

Introduction: A variety of exotic reptiles are kept as “pets” and the ownership of these animals is rising in Hong Kong. Two lizard species are known to be venomous: the Gila monster (Heloderma suspectum) and the Mexican Beaded Lizard (Heloderma horridum). Both of them are native to the North America but are traded in the pet markets. Bites from these lizards are capable of causing severe envenomation in humans. Case presentation: A 41-year-old man presented to the emergency department after bitten by his exotic pet. His right hand was bitten by a Gila monster resulting in local swelling and intense pain. The local envenomation lasted for about 12 hours and then gradually improved. Discussion: Bite by Gila monster could result in local and systemic envenomation. Local envenomation includes intense pain of the injured site, edema and paraesthesia. Systemic envenomation including hypotension and airway edema occurs in severe envenomation. Conclusion: With the increasing popularity of keeping exotic pets in Hong Kong, envenomation by exotic venomous animals may be encountered by the emergency physicians. Knowledge about the potential envenomation effects of these exotic animals is essential for proper management of the patients. [ABSTRACT FROM AUTHOR]

Population genetic baselines for species perceived to be at-risk are crucial for monitoring population trends and making well-informed management decisions. We characterized the genetic status of a population of Gila monsters (Heloderma suspectum), a large venomous lizard native to deserts of the southwestern United States and northern Mexico, by sampling 100 individuals in Sonoran Desert upland habitat at Saguaro National Park, Arizona, USA. We used 18 microsatellite markers, along with 1195 bp of sequence data from the mitochondrial DNA 12S locus, to examine genetic diversity, estimate effective population size, and assess demographic history. Despite suburban development adjacent to the study area, we observed high genetic diversity with uninhibited gene flow within this protected population. We estimated effective population size (Ne) for the total sample area (80 km2) using the linkage disequilibrium method in NeEstimator to be 94 individuals (95% confidence interval: 80.7-111.2). In 2011, we used capture-recapture methods to estimate that 80 adult Gila monsters (95% CI = 37-225) inhabited the area along the 14-km transect that we surveyed most frequently; probability of detecting resident Gila monsters during surveys was <0.01, highlighting the challenges of studying the species. Despite being considered an elusive and thus potentially rare species, these data reveal that in this protected environment the population appears healthy and robust. The results provide an important genetic baseline for future studies and monitoring, and exemplify the success of protective population measures in National Parks and under Arizona state laws. [ABSTRACT FROM AUTHOR]

Down-regulation of the digestive system between large meals is thought to afford energetic benefits to animals that feed infrequently. However, this idea has not been thoroughly tested. Thus, we assessed the realized benefits of infrequent feeding by examining how the timing of meal consumption influenced digestive efficiency and whole-body growth of juvenile Gila monsters, a binge-feeding lizard. All animals in our study received the same total energy intake for each feeding cycle, but meals were distributed differently over time among groups. One group had a 10-14-day period of down-regulation between meal sets while the other group had a constantly activated digestive system. The groups did not show differences in growth; however, differences in digestive efficiency for a specific meal indicate that feeding regime may have caused digestive adjustments (e.g. more efficient digestion) in one treatment group. Overall, our findings show that the energetic benefits of down-regulation may depend more on species, extent of digestive regulation, or duration of fasting than previously supposed. [ABSTRACT FROM AUTHOR]

The morphological origin of the dark and pink-orange areas in the skin of the venomous lizard Heloderma suspectum is not known. Histology and electron microscopy show that dark-grey areas of the skin derived from dermal chromatophores localized in specific areas present underneath the epidermis. A dynamic chromatophoric unit in the dermis is absent. In the darkest areas of the skin, the accumulation of melanosomes in cells of the beta-layer contributes to increase the black intensity. In the orange-pink areas, the superficial dermis contains xantophores storing numerous carotenoid vesicles, rare or absent lamellated pterinosomes and a variable number of melanosomes. These xanto-melanophores predominate over the remaining chromatophores and form a continuous stratum underneath the epidermis. Beneath this lipoid-rich stratum, iridophores are infrequent and do not form a continuous layer in the dermis. In the paler areas of the skin, melanophores are sparse in both superficial and deeper part of the dermis where irregularly oriented bundles of collagen fibrils are present. The prevalent xanto-melanophores localized in the pink-orange areas of the skin contribute to an effective sunlight protection in desert conditions in addition to the darker regions occupied by melanophores. [ABSTRACT FROM AUTHOR]

Background. The Gila monster ( Heloderma suspectum) is a venomous lizard native to the deserts of southwestern United States (US) and northern Mexico. The purpose of this study was to describe human exposures to Gila monsters reported to US poison control centers (PCCs) with a focus on Arizona cases. Methods. The American Association of Poison Control Centers' National Poison Data System (NPDS) was used to access and retrospectively review all calls to US PCCs, concerning Gila monsters between January 1, 2000 and October 31, 2011. In addition, detailed records from the two Arizona PCCs were reviewed for the same time period. Results. A total of 319 calls regarding Gila monsters were identified in the NPDS. Of these, 105 (33%) were human exposures; most (79%) occurred in males. A total of 71 (68%) of these 105 cases were referred to a health care facility (HCF); 30 (29%) were managed on-site. Of the 71 HCF referrals, 36 (51%) were discharged home and 17 (24%) were admitted. Most (65%) admissions were to an intensive care unit (ICU). Arizona's PCCs received 70 unique reports of Gila monster bite. Most (77%) of the bites in Arizona involved an upper extremity. Eight (11%) involved patients under the age of 18 years. Eleven (16%) Arizona cases were work-related. Twenty-eight (40%) of the 70 bites in Arizona were evaluated in a HCF, but not admitted. Eleven (16%) were admitted, of which five were to an ICU. Six patients had edema of airway structures; three required emergent airway management, one by cricothyrotomy. There were no deaths. Conclusion. Gila monster bites are uncommon. Many cases did not require hospitalization. Edema of airway structures is an infrequent, but life-threatening complication. [ABSTRACT FROM AUTHOR]

Research into snake venoms has revealed extensive variation at all taxonomic levels. Lizard venoms, however, have received scant research attention in general, and no studies of intraclade variation in lizard venom composition have been attempted to date. Despite their iconic status and proven usefulness in drug design and discovery, highly venomous helodermatid lizards (gila monsters and beaded lizards) have remained neglected by toxinological research. Proteomic comparisons of venoms of three helodermatid lizards in this study has unravelled an unusual similarity in venom-composition, despite the long evolutionary time (~30 million years) separating H. suspectum from the other two species included in this study (H. exasperatum and H. horridum). Moreover, several genes encoding the major helodermatid toxins appeared to be extremely well-conserved under the influence of negative selection (but with these results regarded as preliminary due to the scarcity of available sequences). While the feeding ecologies of all species of helodermatid lizard are broadly similar, there are significant morphological differences between species, which impact upon relative niche occupation. [ABSTRACT FROM AUTHOR]

A wide variety of sex determination systems exist among squamate reptiles. They can therefore serve as an important model for studies of evolutionary transitions among particular sex determination systems. However, we still have only a limited knowledge of sex determination in certain important lineages of squamates. In this respect, one of the most understudied groups is the family Helodermatidae (Anguimorpha) encompassing the only two venomous species of lizards which are potentially lethal to human beings. We uncovered homomorphic ZZ/ZW sex chromosomes in the Gila monster (Heloderma suspectum) with a highly heterochromatic W chromosome. The sex chromosomes are morphologically similar to the ZZ/ZW sex chromosomes of monitor lizards (Varanidae). If the sex chromosomes of helodermatids and varanids are homologous, female heterogamety may be ancestral for the whole Anguimorpha group. Moreover, we found that the karyotype of the Gila monster consists of 2n = 36 chromosomes (14 larger metacentric chromosomes and 22 acrocentric microchromosomes). 2n = 36 is the widely distributed chromosomal number among squamates. In his pioneering works representing the only previous cytogenetic examination of the family Helodermatidae, Matthey reported the karyotype as 2n = 38 and suggested a different chromosomal morphology for this species. We believe that this was probably erroneously. We also discovered a strong accumulation of telomeric sequences on several pairs of microchromosomes in the Gila monster, which is a trait documented relatively rarely in vertebrates. These new data fill an important gap in our understanding of the sex determination and karyotype evolution of squamates. [ABSTRACT FROM AUTHOR]

Field metabolic rates (FMR) and water influx rates (WIR) were measured in Gila Monsters ( Heloderma suspectum) in the Mojave Desert of southern Nevada. Gila Monsters had rates of energy use that were less than half of those expected for lizards of their size, including species that live in arid habitats. Free-living Gila Monsters also had comparatively low water flux rates. The annual energy requirements of adult Gila Monsters averaged approximately 3,766 kJ, with two-thirds of the total (2,533 kJ) allocated to activity while above ground, and one-third to resting metabolism (1,233 kJ; mostly while below ground). Unusually low rates of resting metabolism caused relative costs of activity to be high: compared to other lizards, Gila Monsters have among the highest proportional use of energy for activity, relative to total energy use. The average annual water expenditure of adults was approximately 775 mL, and lizards achieved positive mass balance by drinking rain water during the late summer monsoon season. Drinking may be critical in meeting annual water requirements. FMR and WIR differed between seasons but were both highest in early summer (mid-May through June), coinciding with the peak of foraging and breeding activities. Levels of above-ground activity significantly influenced both FMR and WIR, whereas body temperature while burrowed influenced only WIR, and body mass (over the range of 270 to 420 g) did not significantly influence either whole-animal FMR or WIR. [ABSTRACT FROM AUTHOR]

Many xeric organisms maintain water balance by relying on dietary and metabolic water rather than free water, even when free water may be available. For such organisms, hydric state may influence foraging decisions, since meal consumption is meeting both energy and water demands. To understand foraging decisions it is vital to understand the role of dietary water in maintaining water balance. We investigated whether meal consumption was sufficient to maintain water balance in captive Gila monsters (Heloderma suspectum) at varying levels of dehydration. Gila monsters could not maintain water balance over long time scales through meal consumption alone. Animals fed a single meal took no longer to dehydrate than controls when both groups were deprived of free water. Additionally, meal consumption imparts an acute short-term hydric cost regardless of hydration state. Meal consumption typically resulted in a significant elevation in osmolality at 6h post-feeding, and plasma osmolality never fell below pre-feeding levels despite high water content (∼70%) of meals. These results failed to support our hypothesis that dietary water is valuable to Gila monsters during seasonal drought. When considered in conjunction with previous research, these results demonstrate that Gila monsters, unlike many xeric species, are heavily reliant on seasonal rainfall and the resulting free-standing water to maintain water balance. [ABSTRACT FROM AUTHOR]

Alibardi, L. and DeNardo, D.F. 2011. Ultrastructural and immunocytochemical features of the epidermis of the lizard Heloderma suspectum indicate richness in lipids and lack of a specialized shedding complex. - Acta Zoologica (Stockholm) 00: 1-9. Abstract The epidermis of the venomous lizard Heloderma suspectum has been studied for detecting generalized and desert adaptations. A thick and non-completely syncytial beta-keratin layer is followed by 60-90 layers of mesos-cells. Non-lamellated or sparse lamellated lipid material is seen among mesos-cells where lipids form the main barrier against water loss. The alpha-layer is made of interlocking cells with irregular perimeter that are connected through desmosomal remnants. Immunocytochemistry shows that beta-keratin is present in beta-cells, disappears in mesos-cells but is diffuse in alpha-cells. Alpha-keratin is seen in mesos-cells but lowers in alpha-cells where alpha-keratin probably mixes with beta-keratin. Although the sequence of layers formed during the renewal stage of the epidermis was not available, a specialized shedding layer with an outer oberhautchen faced to an inner clear layer appears absent in this species. This condition suggests that shedding occurs at the boundary between the outer (old) alpha-layer and the inner (new) beta-layer formed underneath the alpha-layer. The thick mesos layer is likely an efficient adaptation to limit water loss in desert conditions while the poorly specialized shedding complex may suggest a primitive stage in the evolution of the shedding layer in this lizard or a special adaptation to water shortage. [ABSTRACT FROM AUTHOR]

The extant venomous Gila monster and beaded lizards, species of Heloderma, live today in southwestern USA and south along the Pacific coastal region into Central America, but their fossil history is poorly understood. Here we report helodermatid osteoderms (dermal ossicles) from the late Miocene-early Pliocene Gray Fossil Site, eastern Tennessee USA. Twenty-three species of mammals are known from the fauna including abundant Tapirus polkensis, as well as fishes, anurans, salamanders, turtles, Alligator, birds, and snakes. Beaded lizards belong to the Monstersauria, a clade that includes Primaderma + Paraderma + Gobiderma + Helodermatidae (Estesia, Eurheloderma, Lowesaurus, and Heloderma). Osteoderms of lizards in this clade are unique within Squamata; they typically are circular to polygonal in outline, domed to flat-domed in cross-section, have a vermiculate surface texture, are not compound structures, and do not have imbricate surfaces as on many scincomorph and anguid lizards. We review and characterize the osteoderms of all members of Monstersauria. Osteoderms from the cranium, body, and limbs of Heloderma characteristically have a ring-extension (bony flange) at least partly surrounding the dome. Its presence appears to be a key character distinct to all species of Heloderma, consequently, we propose the presence of a ring-extension to be an apomorphy. Three osteoderms from the Gray Fossil Site range from 1.5 to 3.0 mm in diameter, have the circular shape of helodermatid osteoderms with a domed apical surface, and have the ring-extensions, permiting generic identification. Macrobotanical remains from the Gray Fossil Site indicate an oak-hickory subtropical forest dominated by Quercus (oak) and Carya (hickory) with some conifer species, an understorey including the climbing vines Sinomenium, Sargentodoxa, and Vitis. Plant and mammal remains indicate a strong Asian influence. [ABSTRACT FROM AUTHOR]

Background: The Gila monster ( Heloderma suspectum), one of several venomous lizard species in the world, is found within the United States and Mexico and is recognized as an iconic symbol of the American Southwest. Thus, Gila monsters are of growing interest in the captive reptile trade and within zoological and educational institutions. Objectives: The aims of this study were to determine results for CBCs, describe cytochemical reactions in WBCs, and obtain plasma biochemical and protein electrophoresis results from wild-caught and captive-bred H. suspectum. Methods: Ventral tail vein blood samples were obtained from 16 captive (14 wild-caught and 2 captive-bred) Gila monsters. CBCs, RBC morphometric analysis, plasma biochemical analysis, and protein electrophoresis were performed. Leukocytes were stained for peroxidase, Sudan black B (SBB), chloroacetate esterase, napthyl butyrate esterase, and leukocyte alkaline phosphatase, and blood smears were examined for the presence of hemoparasites. Results: The median (range) PCV was 37% (22-50%) and WBC count was 4.6 × 103/μL (3.3-6.4 × 103/μL) with approximately 50% heterophils and fewer lymphocytes, basophils, azurophils, and monocytes in decreasing order. Cytochemical reactions were unique among reptiles with strong staining for peroxidase and SBB in monocytes/azurophils. Biochemical results were similar to those of earlier reports with slight increases in uric acid and urea concentrations. Plasma electrophoretic results indicated that albumin was approximately equal to the combined globulin fractions. Conclusions: Results of blood analysis in healthy wild-caught and captive-bred H. suspectum may be useful for monitoring health status in this species. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide 1 (GLP-1) is a small peptide component of the prohormone, proglucagon, that is produced in the gut. Exendin-4, a GLP-1 receptor agonist originally isolated from the saliva of H. suspectum or Gila monster, is a peptide that shares sequence and functional homology with GLP-1. Both peptides have been demonstrated to stimulate insulin secretion, inhibit glucagon secretion, promote satiety and slow gastric emptying. As such, GLP-1 and Exendin-4 have become attractive pharmaceutical targets as an adjunctive therapy for individuals with type II diabetes mellitus, with several products currently available clinically. Herein we summarize the cell biology leading to GLP-1 production and secretion from intestinal L-cells and the endocrine functions of this peptide and Exendin-4 in humans. Additionally, gene therapeutic applications of GLP-1 and Exendin-4 are discussed with a focus on recent work using the salivary gland as a gene therapy target organ for the treatment of diabetes mellitus. [ABSTRACT FROM AUTHOR]

We fit asymptotic models to growth data of free-ranging Gila Monsters studied near Tucson, Arizona. We used a mixed-effects modeling procedure that allows for unequal numbers of recaptures by accounting for within-individual covariance and models between-individual variation in growth parameters as random effects. A model selection procedure and diagnostic tests indicated that a von Bertalanffy curve with seasonal cessation of growth and a random effect for asymptotic size fit the data best. Young Gila Monsters in our study grew faster than previously reported growth rates from both field and captive animals, and we discuss potential reasons for this discrepancy. [ABSTRACT FROM AUTHOR]

In desert species, seasonal peaks in animal activity often correspond with times of higher rainfall. However, the underlying reason for such seasonality can be hard to discern because the rainy season is often associated with shifts in temperature as well as water and food availability. We used a combination of the natural climate pattern of the Sonoran Desert and periodic water supplementation to determine the extent to which water intake influenced both the behavioral ecology and the physiological ecology of a long-lived desert lizard, the Gila monster (Heloderma suspectutn) (Cope 1869). Water-supplemented lizards had lower plasma osmolality (i.e., were more hydrated) and maintained urinary bladder water reserves better during seasonal drought than did control lizards. During seasonal drought, water-supplemented lizards were surface active a significantly greater proportion of time than were controls. This increased surface activity can lead to greater food acquisition for supplemental Gila monsters because tail volume (an index of caudal lipid stores) was significantly greater in supplemented lizards compared with controls in one of the two study years. [ABSTRACT FROM AUTHOR]

To assess whether urbanization influences the spatial ecology of a rare and protected venomous reptilian predator, the Gila monster Heloderma suspectum, we compared home range (HR) size and movement parameters at three sites varying in degree of urbanization in the Sonoran Desert. We predicted that the urban population of H. suspectum would exhibit smaller HRs, avoid human structures and show less movement. Multivariate analysis indicated that males generally exhibited larger HRs and had higher movement rates and activity levels than females at all three sites. Contrary to our predictions, however, HR size and movement parameters did not vary across the sites in relation to the level of urbanization. At the urban site, individuals often crossed narrow roads and regularly used artificial structures as refuges for extended periods. Furthermore, the population sex ratio at the urban site was female-biased, consistent with the expectation that occupation of larger HRs and higher movement rates results in higher mortality for males in urbanized areas. Gila monsters did not appear to alter certain aspects of their spatial ecology in response to low levels of human activity but additional work will be required to assess population viability and possible effects in the long term and with higher levels of urbanization. [ABSTRACT FROM AUTHOR]

The gastrointestinal tract possesses the capacity to change in form and function in response to fasting and feeding. Such plasticity can be dramatic for species that naturally experience long episodes of fasting between large meals (e.g. sit-and-wait foraging snakes, estivating anurans). By contrast, for active foraging species that feed more frequently on smaller meals, gastrointestinal responses are more modest in magnitude. The Gila monster Heloderina suspectum is an active foraging lizard that feeds infrequently on meals weighing up to one-third of its body mass. Additionally, Gila monsters possess a species-specific salivary peptide, exendin-4, which may be involved in the regulation of metabolic and digestive performance. To investigate the adaptive postprandial response of Gila monsters and the potential regulatory role of exendin-4, we measured metabolic and intestinal responses to feeding in the presence or absence of circulating exendin-4. Following the consumption of rodent or egg meals equivalent to 10% of lizard body mass, metabolic rates peaked at 4.0- to 4.9- fold of standard metabolic rates and remained elevated for 5–6 days. Specific dynamic action of these meals (43–60 kJ) was 13–18% of total meal energy. Feeding triggered significant increases in mucosal mass, enterocyte width and volume, and the upregulation of D-glucose uptake rates and aminopeptidase-N activity. Total intestinal uptake capacity for L-leucine, L-proline and 1)-glucose were significantly elevated within 1–3 days after feeding. Whereas the absence of circulating exendin-4 had no impact on postprandial metabolism or the postprandial response of intestinal structure and nutrient uptake, it significantly increased intestinal aminopeptidase-N activity. Within the continuum of physiological responses to feeding and fasting, Gila monsters occupy an intermediate position in experiencing moderate, though significant, regulation of intestinal performance with feeding. [ABSTRACT FROM AUTHOR]

Animals inhabiting xeric environments use a variety of behavioral and physiological strategies to balance water budgets. We studied the potential contribution of the urinary bladder to osmoregulation in a large desert lizard, the Gila monster Heloderma suspectum. Here we present results of a series of in vivo laboratory experiments which tested the hypothesis that the Gila monster urinary bladder serves as a physiological reservoir, as in amphibians and chelonians, providing water that buffers increases in plasma osmolality when food and water are unavailable. Adult Gila monsters absorbed water from the urinary bladder into circulation and absorption of water from the urinary bladder and drinking water provided similar osmoregulatory benefits within 24 h, although drinking water provided a more immediate osmotic benefit. During food and water deprivation, plasma osmolality increased 2.5 times faster in lizards with an empty urinary bladder compared with those with a full bladder. During rehydration, stereotyped binge drinking behavior increased body mass nearly 22%, which resulted in a 24% reduction in plasma osmolality and a substantial increase in bladder water within 24 h. These results support our hypothesis and demonstrate for the first time in an adult lizard that the urinary bladder can function as a long-term physiological water reservoir. This trait can provide a critical benefit to osmoregulation during the 2- to 3-month summer dry season characteristic of the deserts that Gila monsters inhabit. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The Gila monster Heloderma suspectum is an active forager in an environment that, at times, can be extremely hot and arid. Thus, Gila monsters face extreme thermostatic and hydrostatic demands. For a desert ectotherm routinely risking dehydration, evaporative water loss (EWL) is typically viewed as detrimental. Yet evaporation simultaneously dehydrates and cools an animal. We explored EWL in Gila monsters by measuring cutaneous, ventilatory and cloacal EWL at five ambient temperatures between 20.5°C and 40°C. Our results show that Gila monsters have high EWL rates relative to body mass. Cutaneous EWL underwent a consistent, temperature-dependent increase over the entire range of test temperatures (Q10=1.61, with EWL ranging from 0.378 to 0.954 mg g–1 h–1). Ventilatory EWL did not show a significant temperature-dependent response, but ranged from 0.304 to 0.663 mg g–1 h–1. Cloacal EWL was extremely low and relatively constant between 20.5°C and 35°C, but rose dramatically above 35°C (Q10 >8.3×107, from 0.0008 at 35°C to 7.30 mg g–1 h–1 at 40°C). This steep rise in cloacal EWL coincided with an increasing suppression of body temperature relative to ambient temperature. Dehydration to 80% of initial body mass led to a delay in the onset and an attenuation of the dramatic increase in cloacal EWL. These results emphasize the potential value of EWL for thermoregulation in ectotherms and demonstrate for the first time the role of the cloaca in this process. [ABSTRACT FROM AUTHOR]

1 The receptor for glucagon-like peptide-1 (GLP-1) can be activated by both its physiological hormone and a peptide discovered in the venom of the Gila Monster, exendin-4, which shows promise as an antidiabetic agent. 2 Exendin-4 displays receptor-binding properties not observed for GLP-1. Firstly, exendin-4 can be truncated by up to eight residues at its N-terminus without a significant loss of affinity. Secondly, exendin-4 maintains high affinity for the isolated N-terminal domain of the receptor, suggesting that exendin-4 makes additional contacts with this domain of the receptor, which nullify the requirement for ligand - receptor interactions involving the extracellular loops and/or transmembrane helices of the receptor's core domain. 3 In order to further understand the nature of the receptor-peptide interaction, a variety of full length and truncated peptide analogues were used to quantify the contribution of each distinct region of exendin-4 and GLP-1 to receptor affinity. 4 Our data show that, for both exendin-4 and GLP-1, the primary interaction is between the putative helical region of the peptide and the extracellular N-terminal domain of the receptor. 5 However, we demonstrate that the contribution to receptor affinity provided by the N-terminal segment of GLP-1 is greater than that of exendin-4, white the C-terminal nine residue extension of exendin-4, absent in GLP-1. forms a compensatory interaction with the N-terminal domain of the receptor. 6 We describe a peptide - receptor binding model to account for these data. [ABSTRACT FROM AUTHOR]

Reports on the study which examined the effects of an irrelevant putative masking compound on the ability of a species of gila monster, Heloderma suspectum, to discriminate between prey and non-prey odors. Details of the tests which involved observing the responses of gila monsters to a series of prey odors and a biologically irrelevant masking odor, cologne; Indication that the lizards can discriminate between prey odors and control odors; Importance of surface cues in the foraging of gila monsters.

Five increasingly anionic phospholipases A2 (Pa1 -Pa5) exist in the venom of the lizard Heloderma suspectum. We recently elucidated the sequence of Pa5, the most abundant and most active variant, towards emulsified phosphatidylcholines. Here we present the primary structures of Pa2, Pa3 (subvariants a and b) and Pa4, based on Edman degradation of tryptic, endoproteinase Arg-C and chymotryptic fragments of the reduced and Scarboxymethylated proteins. Pa1-Pa5, considered collectively, belong to an original class of secretory phospholipases A2 with 141-143 residues, a short hydrophobic N-terminus, 10 half-cystine residues and an extended C-terminus. The only known phospholipase A2 with characteristics close enough to be a member of the same class is that present in the venom from the insect Apis mellifera. More specifically, the sequences of Pa3 and Pa5 are almost identical, and those of Pa2 and Pa4 are also quite similar. Both groups diverge enough to indicate the translation of two mRNA species in the venom gland. The primary structure of Pa3 reveals the existence of subvariants a and b, the sequence of which is identical to that previously defined for Pa5, except that the C-terminal tripeptide GEG in Pa5 is replaced by the dipeptide GE in Pa3a and the tetrapeptide GEGR in Pa3b, Pa4 when compared to Pa5, shows 21 substitutions with a cluster of five modified amino acids in positions 40-44, immediately after the catalytic segment amino acids 30-39, and added changes scattered before the C-terminus. Pa2 differs from Pa4 only by the absence of the Gly142 C-terminal residue. The 15% difference in primary structure observed between the Pa3-Pa5 and Pa2-Pa4 subgroups might be largely responsible for their distinct biological properties. [ABSTRACT FROM AUTHOR]

1. Five increasingly anionic variants (Pa1-Pa5) of Ca2+-dependent phospholipase A2 were purified to homogeneity from the venom of the lizard Heloderma suspectum (Gila monster). The purification procedure was based on semi-preparative reverse-phase HPLC followed by anion-exchange HPLC and analytical reverse-phase HPLC. 2. Their Mr were 17 000-18 000, as deduced by SDS/PAGE. Specific activities tested by the capacity to hydrolyze phosphatidylcholines at pH 8.5 decreased as follows: Pa3 > Pa5 > Pa4 > Pa1 > Pa2. These activities showed the same optimum pH (9.0), were mainly of the phospholipase A2 type and were lost upon p-bromophenacyl bromide treatment. 3. All five phospholipases efficiently stimulated amylase release from dispersed rat pancreatic acini at pH 7.4, their potency decreasing as follows: Pa2 > Pa1 ≈ Pa4 > Pa3 ≈ Pa5. No deleterious effect was apparent based on the lack of lactate dehydrogenase release. 4. The five variants, Pa1 - Pa5, differed significantly in amino acid composition and this, together with distinct antigenic properties of Pa2 and Pa5, establishes the subheterogeneity of this new type of phospholipase A2, despite the fact that the N-terminal amino acid sequence (31 residues) of Pa1-Pa5 was exactly the same. 5. The full sequence of the major variant, Pa5, showed that this 142-amino-acid protein exhibited greater similarity to the bee venom enzyme than to any class I or class II secretory phospholipase A2 from snake venom and mammalian pancreas. While Pas displayed the highly conserved region between Asp30 and Cys39 (the essential active site of all phospholipases A2), its salient original points included 10 half-cystine residues only, an incomplete N-terminal sequence, large changes in the putative calcium loop, several alterations after the active site and a C-terminal extension never seen in other phospholipases A2, with the only exception being bee venom. [ABSTRACT FROM AUTHOR]

In order to understand the cutaneous water loss in the desert-adapted and venomous lizard Heloderma suspectum, the microscopic structure and lipid composition of epidermal molts have been examined using microscopic, spectroscopic and chemical analysis techniques. The molt is formed by a variably thick, superficial beta-layer, an extensive mesos-region and few alpha-cells in its lowermost layers. The beta-layer contains most corneous beta proteins while the mesos-region is much richer in lipids. The proteins in the mesos-region are more unstructured than those located in the beta-layer. Most interestingly, among other lipids, high contents of cholesteryl-β-glucoside and cholesteryl sulfate were detected, molecules absent or present in traces in other species of squamates. These cholesterol derivatives may be involved in the stabilization and compaction of the mesos-region, but present a limited permeability to water movements. The modest resistance to cutaneous water-loss of this species is compensated by adopting other physiological strategies to limit thermal damage and water transpiration as previous eco-physiological studies have indicated. The increase of steroid derivatives may also be implicated in the heat shock response, influencing the relative behavior in this desert-adapted lizard. [ABSTRACT FROM AUTHOR]

A 29-year-old man was bitten on the forearm by a wild Gila monster. Radiographs demonstrated subcutaneous air. During a period of observation, erythema and edema progressed from the forearm to the axilla and he developed a significant leukocytosis. No purulence was found upon surgical evaluation. We hypothesize that air was introduced into the wound by the 'pulsing,' chewing-like action that the Gila monster made while it was attached to the man's forearm. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including medical reference intervals in wobbegong sharks, Gila monsters, and bearded dragons, human populations guidelines, and veterinary diagnosis.

A letter to the editor is presented in response to the article "Release of Exendin-4 Is Controlled by Mechanical action in Gila Monsters, Heloderma suspectum," by Carolyn M. Christel and Dale F. DeNardo in the 2006 issue.

The article focuses on the development of a new class of drugs, called incretin mimetics, which improves glycemic control, insulin secretion and markers of beta cell function in patients with type 2 diabetes. Two incretin mimetics are under investigation. One is exenatide, an injectable synthetic version of exendin-4, a hormone found in the saliva of the gila monster that displays properties similar to human glucagons-like peptide 1 (GLP-1), which is the most potent incretin produced in the human gut. An oral incretin mimetic, LAF237, works by blocking the action of dipeptidyl peptidase 4, an enzyme that normally inactivates GLP-1.

The article presents a study whether gila monsters can use water stored in their urinary bladders for hydration.