Effect of Diet-induced Obesity on Glucose and Insulin Tolerance of a Rodent with a Low Insulin Response (Acomys cahirinus)

Abstract

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.

Correction of diabetic pattern of insulin release from islets of the spiny mouse (Acomys cahirinus) by glucose priming in vitro

“…The present findings suggest that a similar situation may exist in Acomys cahirinus. It was indeed shown in a previous study [16] that when insulin resistance was in-235 duced in Acomys by dietary measures, the insulin secretion of the animals was not substantially augmented, and consequently hyperglycaemia developed. Thus, the normoglycaemic Aeomys, whose islets have sluggish insulin response to glucose, may represent a model for prediabetes, namely individuals with increased risk of developing diabetes.…”

“…To elucidate the metabolic defect(s) of the/3 cells, suitable animal models for Type 2 diabetes are needed. The spiny mouse (Acomys cahirinus) is a semi-desert rodent which has been studied extensively as a model for Type 2 diabetes in man [8][9][10][11][12][13][14][15][16]. Bred in captivity, these animals demonstrate various degrees of glucose intolerance, become obese with age and develop hyperglycaemia.…”

“…Bred in captivity, these animals demonstrate various degrees of glucose intolerance, become obese with age and develop hyperglycaemia. At all stages of glucose intolerance, whether obese or lean, bred in captivity or newly captured, the spiny mouse exhibits decreased insulin response to glucose stimulation, both in vivo and in vitro [10][11][12][13][14]16].…”

“…Bred in captivity, these animals demonstrate various degrees of glucose intolerance, become obese with age and develop hyperglycaemia. At all stages of glucose intolerance, whether obese or lean, bred in captivity or newly captured, the spiny mouse exhibits decreased insulin response to glucose stimulation, both in vivo and in vitro [10][11][12][13][14]16].Studies in recent years demonstrated that apart from initiating immediate insulin release, glucose generates a time-dependent state of potentiation in the islets of Langerhans, which leads to the amplification of insulin secretion upon subsequent stimulation [17][18][19][20][21][22]. The present study examines the effect of such glucose priming on insulin release in the islets of spiny mice and demonstrates that it corrects the diabetic pattern of insulin secretion.…”

Nutritionally Induced Diabetes in Desert Rodents as Models of Type 2 Diabetes: Acomys cahirinus (Spiny Mice) and Psammomys obesus (Desert Gerbil)

“…Insulin resistance preceded the hyperglycemia and was associated with mild hyperinsulinemia, progressing with time to more severe serum insulin elevation. Insulin resistance, which is associated with an insulin receptor defect as described in several obese animal species and obese humans was considered to be the cause of overt diabetes in the Geneva spiny mice maintained on the fat-rich seedsupplemented diet (Gutzeit et al 1979). Indeed, a correlation between insulin sensitivity and body fat content was demonstrated (Shafrir and Adler 1984).…”