The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca²⁺ mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca²⁺ mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats.

Key points: The World Health Organization recommends exclusive breastfeeding until 6 months of age as an important strategy to reduce child morbidity and mortality. Studies have associated early weaning with the development of obesity and type 2 diabetes in adulthood. In our model, we demonstrated that early weaning leads to increased insulin secretion in adolescent males and reduced insulin secretion in adult offspring. Early weaned males exhibit insulin resistance in skeletal muscle. Early weaning did not change insulin signalling in the muscle of female offspring. Taking into account that insulin resistance is one of the primary factors for the development of type 2 diabetes mellitus, this work demonstrates the importance of breastfeeding in the fight against this disease. Early weaning (EW) leads to short‐ and long‐term obesity and diabetes. This phenotype is also observed in experimental models, in which early‐weaned males exhibit abnormal insulinaemia in adulthood. However, studies regarding the effect of EW on pancreatic islets are rare. We investigated the mechanisms by which glycaemic homeostasis is altered in EW models through evaluations of insulin secretion and its signalling pathway in offspring. Lactating Wistar rats and their pups were divided into the following groups: non‐pharmacological EW (NPEW): mothers were wrapped with an adhesive bandage on the last 3 days of lactation; pharmacological EW (PEW): mothers received bromocriptine to inhibit prolactin (1 mg/kg body mass/day) on the last 3 days of lactation; and control (C): pups underwent standard weaning at PN21. Offspring of both sexes were euthanized at PN45 and PN180. At PN45, EW males showed higher insulin secretion (vs. C). At PN170, PEW males exhibited hyperglycaemia in an oral glucose tolerance test (vs. C and NPEW). At PN180, EW male offspring were heavier; however, both sexes showed higher visceral fat. Insulin secretion was lower in EW offspring of both sexes. Males from both EW groups had lower glucokinase in islets, but unexpectedly, PEW males showed higher GLUT2, than did C. EW males exhibited lower insulin signalling in muscle. EW females exhibited no changes in these parameters compared with C. We demonstrated distinct alterations in the insulin secretion of EW rats at different ages. Despite the sex dimorphism in insulin secretion in adolescence, both sexes showed impaired insulin secretion in adulthood due to EW.