Decreased glucose tolerance but normal blood glucose levels in the field in the caviomorph rodent Ctenomys talarum: The role of stress and physical activity Federico Vera ⁎, Roxana R. Zenuto, C. Daniel Antenucci 1 Laboratorio de Ecofisiología, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, CC 1245, Mar del Plata, 7600, Argentina ABSTRACT ARTICLE INFO Article history: Received 26 March 2008 Received in revised form 26 June 2008 Accepted 26 June 2008 Available online 29 June 2008 Keywords: Blood glucose regulation Compensatory mechanisms Ctenomys Exercise Glucose tolerance test Hystricomorph rodents Stress Hystricomorph rodents have a divergent insulin molecule with only 1–10% of the biological activity in comparison to other mammalian species. In this study, we used the subterranean rodent Ctenomys talarum as a model and performed blood glucose tolerance tests (GTTs) with trained and untrained individuals to evaluate blood glucose regulation and the possible role of physical activity as a compensatory mechanism. Additionally, we evaluated the variations in blood glucose during acute and chronic stress and gathered data in the field to evaluate natural-occurring variations in blood glucose levels. The GTTs showed that C. talarum have a diminished capacity of regulating blood glucose levels in comparison to other mammals and suggest that unexplored differences in the compensatory mechanisms, insulin structure and/or glucose transporters exist within species of hystricomorph rodents. However, blood glucose levels in the field stayed within the normal mammalian range. Physical activity did not prove to be a compensatory mechanism for blood glucose regulation. The individuals did not display important increases in blood glucose after acute stressors and managed to adequately regulate blood glucose during chronic stress. We suggest that the species may not face a selective pressure favoring a more tightly, mammalian like, capacity of regulating blood glucose levels. © 2008 Elsevier Inc. All rights reserved. 1. Introduction Blood glucose concentration in mammals is tightly regulated as a consequence of its central role in the maintenance of homeostasis and coarsely reflects a trade-off between two opposing hormones: insulin and glucagon. In spite of the high diversity of mammals, insulin is a highly-conservative protein (Chan and Steiner, 2000; Conlon, 2001). In fact, the regulatory properties of this hormone are interchangeable among species. Nevertheless, hystricomorph rodents are an exception among mammals (Conlon, 2001), possessing an insulin molecule with many amino acid substitutions that affect its physiological properties and results in a biological activity of only 1–10% in comparison to non- hystricomorph mammals (King and Kahn, 1981). Their insulin molecule exhibits also changed immunological properties and a higher growth-promoting activity (Zimmerman et al., 1974; King and Kahn, 1981). Despite these atypical physiological properties, hystri- comorph rodents assayed to date are able to regulate blood glycemia like non-hystricomorph mammals (Opazo et al., 2004). In this sense, it is considered that members of this group have developed compensa- tory traits that allow them to achieve standard mammalian blood glucose concentrations, though some of them remain unexplored. These include increases in insulin concentrations, decreased rate of insulin degradation (Zimmerman et al., 1974), increases in receptor numbers (Muggeo et al., 1979; Dufty et al., 2002) and changes in the insulin receptor (Opazo et al., 2004). Two issues related to glucose homeostasis that have not been studied in hystricomorphs are the opposing effects of stress and physical activity on blood glucose concentration. Stress is known to produce a hyperglycemic effect via the activation of both the sympathetic nervous system and the hypothalamic–pituitary–adrenal (HPA) axis (Boonstra, 2005), and has been shown to complicate glucose regulation in patients with diabetes mellitus (Inui et al., 1998, Surwit et al., 2002). Oppositely, a large body of evidence shows that contractile activity per se stimulates glucose uptake into muscle even when insulin is absent by inducing the translocation of the glucose trans- porter GLUT4 from an intracellular pool to the plasma membrane (Hayashi et al., 1997; Bryant et al., 2002; Holloszy, 2003). Thus, muscle contractions have an insulin-like effect on glucose transport, causing the rapid uptake of glucose from the blood (Holloszy, 2003). Due to this reason, it is possible that hystricomorph rodents could use the benefits of exercise as another way to compensate for the low biological activity of their insulin. An interesting model to broaden our knowledge about glucose regulation in hystricomorphs is the subterranean rodent Ctenomys talarum (tuco-tucos), a solitary, highly-aggressive species that inhabits in southern parts of South America (Woods, 1993) and, therefore, belongs to the group of caviomorph rodents. Members of the Ctenomyidae family deserve Comparative Biochemistry and Physiology, Part A 151 (2008) 232–238 ⁎ Corresponding author. Tel.: +54 0223 4757008. CONICET. E-mail address: fvera@mdp.edu.ar (F. Vera). 1 Formerly Antinuchi. 1095-6433/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.cbpa.2008.06.030 Contents lists available at ScienceDirect Comparative Biochemistry and Physiology, Part A journal homepage: www.elsevier.com/locate/cbpa