RÔLE ÉCO-PHYSIOLOGIQUE DE L'INSULINO-RESISTANCE DANS L'ADAPTATION DU MÉTABOLISME ÉNERGÉTIQUE AUX CONDITIONS NATURELLES HYPOCALORIQUES : CAS D'UNE ESPÈCE DÉSERTICOLE, LE PSAMMOMYS OBESUS

摘要

insulinodépendants, ce qui nécessite une sécrétion d'insuline plus importante. Les données obtenues sur l'animal vivant mettent en évidence chez le Psammomys un excès d'insuline circulant physiologique qui lui permet d'activer sa lipogenèse et augmenter le volume de son tissu adipeux (ce qui explique en même temps l'hypoglycémie relative du Psammomys). Les valeurs de l'insulinémie et de la glycémie sont les témoins de cette insu-linorésistance (0,51 ± 0,01 contre 0,86 ± 0,08 g/l de glycémie chez le Psammomys et rat Wistar, respectivement ; alors que l'insulinémie est la même chez les deux espèces : en moyenne de 20μU/ml). Ce phénomène physiologique particulier chez cette espèce déserti-cole explique en partie le rôle eco-physiologique de l'insulino-résistance dans l'adaptation du métabolisme énergétique aux conditions drastiques hypocaloriques de l'environnement désertique.%In this study, we have compared the energetic metabolism of wild adult Psammomys obesus to that of adult Wistar rat. The data obtained shown that energetic homeostasis is lower in Psammomys versus Wistar rat. In the food state, the glycemia, insulinemia, lipemia (triglycerides and total cholesterol) and caloric intake were decreased in Psammomys versus Wistar rat. Respectively, 53%, 36%, 30%, 17% and 42%. After 12 h of fasting, the insulinemia and glycemia are little modified in Psammomys, whereas the triglycerides were decreased in Psammomys versus Wistar rat (73%). Interestingly, the body mass index was not different in the two groups (0.51 ±0.02 vs 0.45±0.01 g/cm~2). Concomitantly, the hepatic glucose production via gluconeogenesis pathway was much lower in Psammomys as compared to Wistar rat (52% of reduction). Maximal gluconeogenic rate was decreased in Psammomys versus Wistar rat (2.39±0.30 vs 5.06±0.30 umol.min-1 .g dry cells-1, respectively). However the intracellular gluconeogenic intermediates (oxaloacetate, phosphoenol-pyruvate, 3-phosphoglycerate, fructose 6-phosphate and glucose 6-phosphate) are not very different between the two species, except for the concentrations of mitochondrial oxaloacetate and malate which appear increased in Psammomys versus Wistar rat. We conclue that hepatic glucose production in Psammomys is curbed due to the inhibition of hydrolysis of glucose 6P into free glucose. In the natural environment, Psammomys is a fatty rodent. This fact explains an energy metabolism orientated towards high lipogenie. Thus, we propose that glucose 6P was deviated from gluconeogenesis to the pentose phosphates pathway, producing NADPH_2 essential to fatty acids biosynthesis. Similarly, the oxaloacetate and mitochondial malate are deviated from gluconeogenesis to the lipogenic pathway via the malic enzyme, which also produces NADPH_2. These two metabolic pathways are lipogenic insulinodependant and required greater insulin secretion. The excess of insulin increases fat deposition in adipose tissue which also explains the hypoglycemia). Moreover, the insulin resistance state is supported by the values of glycemia (0.51 ± 0.01 versus 0.86± 0.08 g/l in Psammomys and Wistar rat, respectively) and insulinemia (20μU/ml in both species). This particular eco-physiological phenomenon in Psammomys explains the role of insulin resistance in energetic metabolism adaptation to the drastic hypocaloric conditions of the desert environment.