No abstract

A technique was developed to permit estimation of intravenous glucose tolerance and the concomitant immunoreactive insulin (IRI) response in the Geneva colony of the semi-desert rodent Acomys cahirinus. Following intravenous injection of glucose 1.5 g/kg, young Acomys (2-3 months, 25-35g body weight) had a significantly lower glucose tolerance (p<0.01) and a smaller 30 rain integrated plasma IRI response (p < 0.001) than age and weight matched albino mice. With increasing age (8 and 21 months) and body weight (57 to 100 g) of the Acomys, glucose tolerance and plasma IRI response decreased further, and in the 21 month old group there were 2 overtly diabetic animals. There was a significant negative correlation between intravenous glucose toleraa:ce and body weight in older Acomys. The results suggest that pancreatic B-cell responsiveness to glucose is impaired in Acomys of all ages, and that this is associated with poor glucose tolerance which may be aggravated by obesity.

Summary. Immunoreactive insulin (11%1) release from collagenase isolated pancreatic islets of spiny mice (Acomys cahirinus) was examined in 15 rain and 2 h incubations at glucose concentrations between 2.8 and 56 mlVi. The resultant glucose-insulin dose-response curves for Acomys islets were compared to those for similarly incubated rat. islets. After 15 mill incubations, IgI release from Acomys islets was significantly lower than that from rat islets at all stimulating glucose concentrations. After 2 h incubations, however, maximal responses were similar for Acomys and rat islets, whereas the sensitivity of Aeomys islets to glucose was significantly less. Cyclic AMP 10 raM, theophylline 5 raM, arginine 10 raM, and cytochalasin B 10 Exg/ml, all enhanced IRI release in the presence of glucose 16.7 mM to a relatively greater extent from Acomys than from rat islets. Vineristine 10-SM reduced II~I release from both Acomys and rat islets, and this to a similar extent. The results suggest that defective IRI release from Acomys islets may be the expression of decreased B-cell sensitivity to glucose, even though Ii~I release from Acomys islets may improve in time with continued exposure to elevated glucose concentrations.The ability of B-cells of Acomys to recognize other agents that enhance the action of glucose appeared unaltered.

In order to characterize pancreatic beta cell function in Geneva bred spiny mice (acomys cahirinus), the dynamics of immunoreactive insulin release were examined during perifusion of pancreatic islets isolated from normoglycemic acomys. The initial insulin response of acomys was slow: no clear-cut early (1 to 10 min) peak of insulin release was observed when glucose in the perifusion medium was abruptly raised from 2.8 mM to concentrations as high as 56 mM. This was true for islets of either young, or older more obese acomys. However, after 20 to 30 min of perifusion at the high glucose concentrations, the rate of insulin release from acomysislets became similar to that from islets of rats or mice. By contrast, glucose-induced insulin release responses observed with islets of Wistar-derived rats, Swiss albino mice, and inbred C57BL/6J lean or obese (ob/ob) mice, were clearly biphasic. Tolbutamide 1.5 mM, arginine 16 mM, and theophylline 10 mM were ineffective in stimulating insulin release from acomys islets in the presence of a substimulatory glucose concentration (2.8 mM), whereas these agents were effective in rat islets at the same substimulatory concentration of glucose. On the other hand, when these agents, as well as cyclic AMP 10 mM or cytochalasin B 10 mug/ml were applied in the presence of a stimulating concentration of glucose (16.8 mM), the glucose-stimulated insulin release from acomys islets was increased to the same or to a greater extent than from rat islets. It is suggested that the failure of all the agents tested to stimulate an early rapid phase of insulin release from acomys islets may be secondary to the observed initial insensitivity to glucose, which insensitivity may in turn reflect a selective impairment in the recognition of glucose as an insulinogenic signal in this species.

Spiny mice (Acomys cahirinus) from the Geneva colony tend to develop diabetes, whereas those maintained in Jerusalem do not. The role of environmental factors in the development of glucose intolerance was investigated by diet exchanges in specimens from the two colonies. Spiny mice on the Geneva diet (laboratory chow supplemented by a seed mixture containing 15% fat by weight) developed massive obesity over 8-10 months; body lipid content increased threefold compared with albino mice and was twofold higher than in spiny mice maintained on the laboratory chow in Jerusalem or in spiny mice living in their natural habitat near the Dead Sea. Spiny mice from the Geneva colony, kept on the laboratory chow alone, were as lean as animals from the Jerusalem colony. Similarly, Jerusalem Acomys given pellets supplemented by seeds developed marked obesity. Liver and adipose tissue enzymes in spiny mice transferred to the seed-supplemented diet showed adaptation typical for fat feeding: decrease in the capacity of glycolysis, NADPH generation, and fatty acid synthesis.The obesity was associated with insulin resistance, evident from a negative correlation between the extent of hypoglycemia after i.v. insulin administration and body lipid content. The glucose disappearance rate (K value) was significantly reduced by obesity, but the insulin response to i.v. glucose increased only moderately. In all the Acomys groups studied, insulin response to i.v. glucose was markedly lower in comparison with the response in albino mice.The following conclusions are drawn: (1) Low insulin response to glucose is a species-characteristic of spiny mice whether the animals are bred in laboratories or live in freedom. (2) Given an appropriate diet, spiny mice develop obesity, accompanied by pronounced insulin resistance. (3) Obesity may be one of the causes of the marked islet hyperplasia in laboratory-kept spiny mice, but this does not result in increased insulin output. (4) The inability of spiny mice to respond with augmented insulin secretion when insulin efficiency is reduced may be responsible for the accelerated development of glucose intolerance in this species. Thus, the liability of Geneva spiny mice to develop diabetes may be caused by the obesity-inducing diet used in this colony rather than to a specific genetic characteristic. (5) The fact that insulin resistance in spiny mice occurs without the development of hyperinsulinemia suggests that similar mechanisms may operate in the development of glucose intolerance in human, low, insulin responders. DIABETES 28:777-784, August 1979.