Low rate of glucose 6-phosphate hydrolysis in liver cells is a physiological feature of non-diabetic wild sand rats (Psammomys obesus)

Objective: In this study we have compared glucose metabolism and liver gluconeogenesis in wild adult desert gerbil Psammomys obesus fed with their natural halophilic plants and Wistar rats fed on a laboratory chow. Psammomys obesus is a natural model of insulin resistance when fed a rodent laboratory chow. Methods: Basal glucose and insulin were determined in plasma of fasting animals. Hepatocyte gluconeogenesis from lactate-plus-pyruvate was investigated in perifused hepatocytes by assessing simultaneously glucose synthesis rate and intracellular oxaloacetate, phosphoenolpyruvate, 3-phosphoglycerate, fructose 6-phosphate and glucose 6-phosphate (G6P) under true steady state conditions. Results: Fasting blood glucose (2.8 +/- 0.1 vs 4.8 +/- 0.4 mmol.L-1) and plasma insulin concentration (129 +/- 14 vs 150 +/- 21 pmol.L-1) were significantly lower in Psammomys as compared to albino rats. Maximal gluconeogenic rate was also lower in Psammomys (2.3 +/- 0.3 vs 5.1 +/- 0.3 mumol.min(-1).g dry cells(-1)). This effect was related to a slower hydrolysis of G6P. Conclusion: A lower G6P hydrolysis in Psammomys as compared to wistar was the main difference between the two groups of liver cells. Such feature may represent the major metabolic adaptation permitting Psammomys to survive despite its severe restrictive natural conditions. Indeed, a low G6P hydrolysis allows an insulin resistance state, with a high lipogenic activity, but associated with low blood glucose. The rise in blood glucose occurring when Psammomys are fed with exogenous carbohydrates perturbs such delicate metabolic equilibrium; resulting thus in a diabetic state because of the deleterious effect of hyperglycemia.