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