0080 : Involvement of the sympathetic nervous system in the development of carbohydrate metabolism disorders

Abstract

The causal role of sympathetic nervous system in the development of metabolic disorders has not been clearly defined. The aim of the study was to determine if a chronic increase of the sympathetic nervous activity can induce and/or accelerate the development of glucose metabolism disorders. For that purpose, we used a transgenic mouse model, in which the gene encoding for the reuptake norepinephrine transporter (NET) has been deleted; these animals display increased urinary catecholamine levels. Carbohydrate homeostasis (intraperitoneal glucose tolerance test, IPGTT, insulin tolerance test, ITT, insulin rates) was studied in heterozygous NET knockout mice (±) or wild-type mice (+/+) at 10, 20 and 25 weeks old. Mice were then fed either with normal chow or 30% w/v fructose in drinking water; glucose metabolism was assessed again after 15 weeks of such diet. Heterozygous mice displayed glucose intolerance already at 10 weeks old (area under the curve of the IPGTT (AUC; %) = 24859 vs 18016, p=0.004); similar results were obtained at 25 weeks old, i.e, just before starting the fructose diet: AUC = 24524 vs 20573, p=0.005 for ± and +/+ mice respectively. Moreover sensibility to insulin seemed to be diminished in ± mice compared to +/+ mice (insulin rate = 1.12 vs 0.86 μg/L and HOMAIR= 11.1 vs 8.4). Heterozygous animals were also much more sensitive to high fructose, since a 20% increase in the AUC of the IPGTT was obtained at the end of the high fructose diet, compared to the 2% increase in +/+ mice. This was associated with a decrease of insulin sensibility (HOMA-IR of ± mice = 11.1 vs 18.1, p=0.01, before and after fructose diet respectively). Our data show that constitutive chronic sympathetic hyperactivity can induce the early development of carbohydrate metabolism disorders. Moreover, it seems to represent a major factor of susceptibility to diet-induced metabolic dysfunction. The author hereby declares no conflict of interest