Poor pubertal protein nutrition disturbs glucose-induced insulin secretion process in pancreatic islets and programs rats in adulthood to increase fat accumulation

Similar to gestation/lactation, puberty is also a critical phase in which neuronal connections are still being produced and during which metabolic changes may occur if nutrition is disturbed. In the present study we aimed to determine whether peripubertal protein restriction induces metabolic programming. Thirty-day-old male rats were fed either a low protein (LP group) diet (4% w/w protein) or a normal protein (NP group) diet (23%) until 60 days of age, when they received the NP diet until they were 120 days old. Body weight (BW), food intake, fat tissue accumulation, glucose tolerance, and insulin secretion were evaluated. The nerve electrical activity was recorded to evaluate autonomous nervous system (ANS) function. Adolescent LP rats presented hypophagia and lower BW gain during the LP diet treatment (P < 0.001). However, the food intake and BW gain by the LP rats were increased (P < 0.001) after the NP diet was resumed. The LP rats presented mild hyperglycemia, hyperinsulinemia, severe hyperleptinemia upon fasting, peripheral insulin resistance and increased fat tissue accumulation and vagus nerve activity (P < 0.05). Glucose-induced insulin secretion was greater in the LP islets than in the NP islets; however, the cholinergic response was decreased (P < 0.05). Compared with the islets from the NP rats, the LP islets showed changes in the activity of muscarinic receptors (P < 0.05); in addition, the inhibition of glucose-induced insulin secretion by epinephrine was attenuated (P < 0.001). Protein restriction during adolescence caused high-fat tissue accumulation in adult rats. Islet dysfunction could be related to an ANS imbalance.