Metabolic Imprinting by Maternal Protein Malnourishment Impairs Vagal Activity in Adult Rats

Protein restriction during lactation has been suggested to diminish parasympathetic activity, whereas sympathetic activity is enhanced in adult rats. The present study analyses whether dysfunction of the autonomic nervous system is involved in the impairment of insulin secretion from perinatally undernourished rats. Male neonates were reared by mothers fed a low- (4%) protein (LP group) or normal- (23%) protein diet (NP group). At 81 days of age, LP rats showed less body mass than NP rats (318 +/- 4 g versus 370 +/- 5 g) (P < 0.001). Fat tissue accumulation decreased in LP [0.8 +/- 0.03 g/100 g body weight (BW)] compared to NP rats (1.1 +/- 0.04 g/100 g BW) (P < 0.001). LP were glucose-intolerant as registered by the area under the curve of an i.v. glucose tolerance test (37 +/- 3) compared to NP rats (29 +/- 2) (P < 0.05); however, LP animals showed fasting normoglycaemia (LP, 5.0 +/- 0.1; NP, 4.9 +/- 0.03 mm) and hypoinsulinaemia (LP, 0.10 +/- 0.02 ng/ml; NP, 0.17 +/- 0.02 ng/ml). LP also showed glucose tissue uptake 60% higher than NP rats (P < 0.05). Vagus firing rate from LP was lower (7.1 +/- 0.8 spikes/5 s) than that in NP rats (12.3 +/- 0.7 spikes/5 s) (P < 0.001); however, there was no difference in sympathetic nervous activity. The cholinergic insulinotrophic effect was lower in pancreatic islets from LP (0.07 +/- 0.01 ng/min/islet) than in NP rats (0.3 +/- 0.06 ng/min/islet), whereas the levels of adrenaline-mediated inhibition of glucose-induced insulin release were similar. Perinatal protein restriction inhibited the activity of the vagus nerve, thus reducing the insulinotrophic effect of parasympathetic pathways on pancreatic beta-cells, which inhibit insulin secretion.