Nutritionally induced diabetes in desert rodents as models of type 2 diabetes: Acomys cahirinus (spiny mice) and Psammomys obesus (desert gerbil)

The dietary effects of hyperglycemia increasingly result in type 2 diabetes in humans. Two species, the spiny mice (Acomys cahirinus) and the desert gerbil (Psammomys obesus), which have different metabolic responses to such effects, are discussed. Spiny mice exemplify a pathway that leads to diabetes without marked insulin resistance due to low supply of insulin on abundant nutrition, possibly characteristic of a desert animal. They respond with obesity and glucose intolerance, beta-cell hyperplasia, and hypertrophy on a standard rodent diet supplemented with fat-rich seeds. The accompanying hyperglycemia and hyperinsulinemia are mild and intermittent but after a few months, the enlarged pancreatic islets suddenly collapse, resulting in loss of insulin and ketosis. Glucose and other secretagogues produce only limited insulin release in vivo and in vitro, pointing to the inherent disability of the beta-cells to respond with proper insulin secretion despite their ample insulin content. On a 50% sucrose diet there is marked lipogenesis with hyperlipidemia without obesity or diabetes, although beta-cell hypertrophy is evident. P.obesus is characterized by muscle insulin resistance and the inability of insulin to activate the insulin signaling on a high-energy (HE) diet. Insulin resistance imposes a vicious cycle of Hyperglycemia and compensatory hyperinsulinemia, leading to beta-cell failure and increased secretion of proinsulin. Ultrastructural studies reveal gradual disappearance of beta-cell glucokinase, GLUT 2 transporter, and insulin, followed by apoptosis of beta-cells. Studies using the non-insulin-resistant HE diet-fed animals maintained as a control group are discussed. The insulin resistance that is evident to date in the normoglycemic state on a low-energy diet indicates sparing of glucose fuel in muscles of a desert-adapted animal for the benefit of glucose obligatory tissues. Also discussed are the effect of Psammomys age on the disabetogenicity of the HE diet; the impaired function of several components of the insulin signal transduction pathway in muscles, which reduces the availability of GLUT4 transporter; the testing of several antidiabetic modalities for the prevention of nutritional diabetes in Psammomys; and various complications related to the diabetic condition.     

Differential energy costs of winter acclimatized common spiny mice Acomys cahirinus from two adjacent habitats

The common spiny mouse Acomys cahirinus, of Ethiopian origin, has a widespread distribution across arid, semi-arid and Mediterranean parts of the Arabian sub-region. We compared the daily energy expenditure (DEE), water turnover (WTO) and sustained metabolic scope (SusMS=DEE/resting metabolic rate) of two adjacent populations during the winter. Mice were captured from North- and South- facing slopes (NFS and SFS) of the same valley, comprising mesic and xeric habitats, respectively. Both DEE and SusMS winter values were greater in NFS than SFS mice and were significantly greater than values previously measured in the summer for these two populations in the same environments. However, WTO values were consistent with previously established values and were not significantly different from allometric predictions for desert eutherians. We suggest that physiological plasticity in energy expenditure, which exists both temporally and spatially, combined with stable WTO, perhaps reflecting a xeric ancestry, has enabled A. cahirinus to invade a wide range of habitats.     

Ultrastructure of Kolmer's crystalloid in the pinealocytes of the common spiny mouse (Acomys cahirinus dimidiatus)

Light-and electron-microscopical observations revealed a rod-like inclusion body in the pinealocytes of the common spiny mouse (Acomys cahirinus dimidiatus). Ultrastructurally, the body is composed of a varying number of tubes whose wall consists of thin filaments aligned in helical arrangement. The inner and outer surface of the wall is covered with ribosome-like granules. Based on a morphological analysis it is concluded that the body described in the present investigation is identical with Kolmer's crystalloid of horizontal cells in the human and primate retina.This work represents a portion of a doctoral thesis (Dr. med.) submitted to the University of Bonn and was presented at the 87th meeting of the anatomische Gesellschaft in Mainz, Germany, March 1992     

The reproductive tract of the male spiny mouse (Acomys cahirinus) and coagulation studies with other species

The testes of the spiny mice showed asymmetry, the left being significantly heavier than the right (P = 0.025). Histological studies indicated that spermatozoa were first present in the testes of animals 35--45 days of age but the maturation of the accessory glands, especially the lateral prostates and coagulating glands, occurred later. The highest fructose concentration in the adult was in the lateral prostates (126.97 +/- 22.23 mg fructose/100 g, n = 5) and coagulating glands (99.38 +/- 17.65 mg fructose/100 g gland weight, n = 5). Coagulation tests of mixtures of extracts of seminal vesicles and coagulating glands from spiny mice and rats indicated that the vesiculase of the spiny mouse was active on rat substrates and vice versa. Cross-reactions of extracts of house mouse (Mus musculus), hamster (Mesocricetus auratus), gerbil (Meriones unguiculatus), and guinea-pig (Cavia porcellus) seminal vesicles (substrate) and coagulating glands (vesiculase) with those of rats and spiny mice showed that although the substrates of rat and spiny mouse were readily coagulated by vesiculase from all the other species, rat and spiny mouse vesiculase were not equally active on substrates of the other species.     

Opioid modulation of ingestive behaviors in the spiny mouse (Acomys cahirinus)

Feeding and drinking behavior were studied in deprived or sated spiny mice (Acomys cahirinus) at various time intervals following peripheral administration of naloxone hydrochloride and butorphanol tartrate. Naloxone attenuated both food and water intake, but not latency to respond, indicating existence of functional opioid-sensitive feeding and drinking systems in this species. Butorphanol tartrate, a mixed opioid agonist/antagonist produced a dose-related enhancement or suppression of feeding, the former naloxone reversible, but had no measureable effect on drinking.     

The structure of the spiny mouse (Acomys cahirinus) ovary during development

The study presents the structure of the ovaries of the spiny mouse (Acomys cahirinus) during the first months of life. The ovaries in neonate females exhibit a large number of primordial and primary follicles, sometimes clustered in nests. The growing follicles were also observed within the ovary at that period. The first, early antral follicles appeared in the ovary during the second week of life. In the group of 60-day old females, the structure of the ovaries was characterized by a significant increase in the connective tissue elements. Moreover, ovarian follicles at various stages of development were observed, except for the antral ones with cumulus oophorus. The first mature follicles were identified in 3-month old females. In the ovarian follicles, apoptosis occurs at all stages of follicle development, especially in the early antral follicles. In the atretic follicles, apoptotic cells were identified in the layer of granulosa cells.     

Intestinal helminths of spiny mice (Acomys cahirinus dimidiatus) from St Katherine's Protectorate in the Sinai, Egypt

Spiny mice, Acomys cahirinus dimidiatus, inhabiting the wadis close to St Katherine in the mountains of the Sinai peninsula, were trapped and their helminth parasites were studied. Sixty one mice provided faeces for analysis and 27 were killed and autopsied. Six species of helminths were recorded (the spirurid nematodes, Protospirura muricola (74.1%) and Mastophorus muris (11.1%), the oxyuroid nematodes, Dentostomella kuntzi (59.3%), Aspiculuris africana (3.7%), and Syphacia minuta (3.7%) and the hymenolepidid cestode Rodentolepis negevi (18.5%)). The spirurids were the dominant species present, accounting for up to 0.87% of total host body weight. Analysis of worm weights and lengths suggested that transmission had been taking place in the months preceding our study. No sex difference in the prevalence or abundance of spirurids was detected. Significant differences were identified in the abundance of total nematode burdens and the mean helminth species richness between the three wadis which provided multiple captures of mice. There was also a marked effect of host age on both parameters. A highly significant positive correlation between spirurid egg counts and total worm biomass indicated that non-invasive techniques based on egg counts could be used to quantify worm burdens and when this technique was applied to a larger sample size (n = 61), a significant difference between sites but no host sex or age effects were detected for spirurid faecal egg counts. The data suggest that there are differences between helminth component communities infecting spiny mice in different neighbouring wadis, a hypothesis which will be explored further through our continuing studies in the Sinai.     

A differential response in the reproductive system and energy balance of spiny mice Acomys populations to vasopressin treatment

Increased dietary salinity suppressed reproduction of the xeric adapted golden spiny mouse, Acomys russatus. Testicular and uterine mass were reduced, suppressed spermatogenesis and vaginal closure were observed. The anti-diuretic hormone, vasopressin (VP), was suggested to mediate such effects. However, increased dietary salinity did not affect reproductive status of a mesic adapted population of the common spiny mouse, A. cahirinus. In the present study, the effect of exogenous VP on the reproductive status and energy balance of both males and females of A. russatus and of a mesic population of A. cahirinus was tested. Vasopressin (Sigma, 50 µg/kg) was injected intraperitoneally in three-day intervals for four weeks. In VP-treated A. russatus, spermatogenesis was significantly suppressed while the change in testis mass did not show significant difference. Both control and VP-treated females lost body mass (W_b) significantly and the latter also exhibited a higher energy expenditure compared to their male counterparts. VP did not affect reproductive status in both sexes of A. cahirinus. Also it did not have a significant effect on W_b, energy intake, and energy expenditure in this species. Our results support the idea that VP mediates the effects of increased diet salinity on reproduction in A. russatus. The results also reinforce previous knowledge that different physiological systems could be integrated by a single biochemical signal.     

Seasonal changes in reproductive development in male spiny mice (Acomys spinosissimus) from South Africa

Seasonal reproduction is a common characteristic of many small mammals which inhabit seasonal environments in temperate regions, the sub-tropics as well as the tropics. It is important for an animal to reproduce during the most favourable time of the year to ensure the survival of the young and maximize reproductive success. In southern Africa, female spiny mice (Acomys spinosissimus) breed during the warm and wet spring and summer months, whereas the reproductive pattern of males is unknown although an opportunistic breeding pattern has been implicated. We investigated testes mass and volume, seminiferous tubule diameter, spermatogenesis and plasma testosterone concentrations in a South African population of male spiny mice on a 2-monthly basis over one year. Testes mass and volume started to increase in July/August and was high from September until December. Seminiferous tubule diameter and spermatogenesis increased during the same months. Plasma testosterone concentration was elevated from July/August to November/December. Development of the reproductive characteristics of male spiny mice was correlated with high rainfall and high ambient temperatures, but reproductive development had already started during the dry season and the coldest months. This shows that reproductive development in males may not be dependent on climatic conditions, and other factors, such as photoperiod, may trigger the onset of reproduction. The data, however, suggest that A. spinosissimus is a true seasonal breeder with reproduction confined to the spring and summer months in southern Africa.     

Significance of anomalous thermoregulation in the pre-diabetic spiny mouse (Acomys cahirinus): cold tolerance: blood glucose and food consumption responses to environmental heat

Decreased cold tolerance, reduced food requirement for body weight maintenance and comparative resistance to the hypoglycaemic effect of fasting in high ambient temperatures have been demonstrated in the spiny mouse. These phenomena could be related to anomalous spiny mouse thermoregulation, a phenomenon which is common in desert rodents and is simulated by mutant and artificially diabetic rodent species. The data can be interpreted as showing evidence for a survival advantage of genotypes with potential diabetic expression, and may provide an explanation of the geographic distribution of certain species.     

Comparative non-shivering thermogenesis in adjacent populations of the common spiny mouse (Acomys cahirinus) from opposite slopes: the effects of increasing salinity

We compared non-shivering thermogenesis between two adjacent populations of the common spiny mouse Acomys cahirinus from different habitats, in relation to increasing salinity. Individuals were captured from the north- and south-facing slopes of the same valley, that represent "Mediterranean" and "desert" habitats, respectively. We hypothesized that the two populations of mice would differ in their thermoregulatory capacities, reflecting their need to cope with the environmental stress in each habitat. We measured resting metabolic rate by recording oxygen consumption, body temperature and response to an injection of exogenous noradrenaline. Mice were maintained on diets with increasing levels of salt intake to examine their abilities to cope with increasing osmotic stress. Mice from north-facing slopes generally had a higher resting metabolic rate and a higher increase in oxygen consumption in response to noradrenaline than mice from south-facing slopes. Increasing salinity decreased resting metabolic rate values, body temperature, and oxygen consumption in response to noradrenaline in both populations, and diminished slope-dependant differences. We suggest that these differences could be a result of an ongoing adaptive process to different climatic conditions, typical of the Mediterranean region, that are a demonstrable example of evolution in action.     

Local variation in helminth burdens of Egyptian spiny mice (Acomys cahirinus dimidiatus) from ecologically similar sites: relationships with hormone concentrations and social behaviour

Populations of Egyptian spiny mice (Acomys cahirinus dimidiatus) in a fragmented montane wadi system in the Sinai showed significant differences in the abundance of gut helminths. Differences in parasite load between populations were positively associated with measures of androgen activity but showed no significant relationship with glucocorticoid activity. Social discrimination tests with adult males from different wadis showed that those from sites with greater helminth abundance were less likely to investigate odours from other males and were less aggressive when subsequently interacting with the odour donors. Subjects showed markedly more investigation towards the odours of males from distant wadis compared with those from their own or immediately neighbouring wadi, but were less aggressive when confronted with odour donors from distant wadis. Despite this, there was a positive relationship between the amount of investigation towards distant male odour and subsequent aggression towards the male. While aggressiveness was positively associated with measures of androgen and glucocorticoid activity, no significant relationship emerged with individual helminth infection. Thus aggressiveness appeared to relate to overall local population levels of infection rather than individual challenge.     

Sex-differences in the Agonistic Behavior of Spiny-mice (Acomys cahirinus)

Observations of 8 groups each containing three adult spiny mice (Acomys cahirinus) revealed that instances of chasing and physical displacement were quite common, while fighting and biting were rarely observed. The relationships between the most frequent behavioral categories were presented in a correlation matrix. In a second, study, ♀♀ tested in their home cages were dominant over ♂♂ In the ♂♂ home cages, however, no differences in the frequency of ♀ vs. ♂ aggression were observed. More instances of aggression were observed in the cages of the ♀♀ than in the cages of the ♂♂.