No abstract

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 β-cells, which inhibit insulin secretion.

Background/Aims: Metabolic syndrome has been identified as one of the most significant threats to human health in the 21^st century. Exercise training has been shown to counteract obesity and metabolic syndrome. The present study aimed to investigate the effects of moderate exercise training on pancreatic beta-cell function and autonomic nervous system (ANS) activity in rats fed a high-fat diet (HFD). Methods: Weaning rats were divided into four groups: rats fed a standard chow or HFD (sedentary, Control-SED and HFD-SED; or exercised, Control-EXE and HFD-EXE, respectively). Exercised rats ran (from 21- to 91-days-old) for 60 minutes (3 times/week) over a 10-week period. Glucose and insulin tolerance tests were performed. Pancreatic islets were isolated to study glucose-induced insulin secretion (GIIS). Parasympathetic and sympathetic nerve electrical signals were measured, and liver samples were processed and histologically analyzed. Results: Exercise prevented obesity, insulin resistance, and liver steatosis as well as improved total cholesterol, ALT, and AST levels. Islets from HFD rats showed insulin hypersecretion which was ameliorated by exercise. Exercise decreased vagal nerve activity in the HFD-EXE group and increased the activity of the sympathetic nervous system in both exercised groups. Conclusion: Exercise prevents obesity and liver steatosis and restores pancreatic beta-cell function and ANS activity in HFD-obese rats.

Disruption of insulin secretion and clearance both contribute to obesity-induced hyperinsulinemia, though reduced insulin clearance seems to be the main factor. The liver is the major site for insulin degradation, a process mainly coordinated by the insulin-degrading enzyme (IDE). The beneficial effects of taurine conjugated bile acid (TUDCA) on insulin secretion as well as insulin sensitivity have been recently described. However, the possible role of TUDCA in insulin clearance had not yet been explored. Here, we demonstrated that 15 days treatment with TUDCA reestablished plasma insulin to physiological concentrations in high fat diet (HFD) mice, a phenomenon associated with increased insulin clearance and liver IDE expression. TUDCA also increased IDE expression in human hepatic cell line HepG2. This effect was not observed in the presence of an inhibitor of the hepatic membrane bile acid receptor, S1PR2, nor when its downstream proteins were inhibited, including IR, PI3K and Akt. These results indicate that treatment with TUDCA may be helpful to counteract obesity-induced hyperinsulinemia through increasing insulin clearance, likely through enhanced liver IDE expression in a mechanism dependent on S1PR2-Insulin pathway activation.

The aim of this study was determine whether the introduction of a high-fat diet during the peripubertal phase induces significant changes in body weight control, glucose homeostasis and the parasympathetic tonus compared with the administration of this diet to adult rats. High-fat diet was offered to male Wistar rats at weaning or during adulthood. A group of rats received high-fat diet for 60 days, from weaning to 81-day-old (HF81) or from 60 to 120-day-old (HF120), whereas 2 other groups received a normal-fat diet (i. e., NF81 and NF120). We analyzed adiposity, glucose homeostasis, insulin sensitivity, and vagal nerve activity. High-fat diet increased the accumulation of adipose tissue in all of the rats, but the difference was greater in the rats that were fed the high-fat diet since weaning (p<0.001). The HF rats showed glucose intolerance with high levels of insulin secretion during the glucose tolerance test (p<0.01). Rats that were fed the high-fat diet presented severe insulin resistance, indicated by a low K itt (p<0.01). Interestingly, the HF81 rats exhibited greater insulin resistance compared with the HF120 rats (p<0.05). The recordings of vagus nerve activity showed that the HF rats had higher parasympathetic activity than the NF rats irrespective of age (p<0.01). Our results show that a high-fat diet offered to rats just after weaning or in adulthood both cause impairment of glycemic homeostasis and imbalance in parasympathetic activity. Importantly, the consumption of high-fat diet immediately after weaning has more drastic consequences compared with the consumption of the same diet during adulthood.