This study investigated the effects of a novel bombesin-related peptide (BR-b), derived from the skin of the Chaco tree frog (Boana raniceps), on glucose homeostasis in non-obese and hypothalamic-obese male rats. Hypothalamic obesity was induced in neonatal rats through high-dose administration of monosodium glutamate (MSG
4 g/kg), while control animals (CTL) received an equimolar saline solution. At 70 days of age, both MSG and CTL groups underwent an oral glucose tolerance test (OGTT
2 g/kg) with or without prior intraperitoneal administration of BR-b at doses of 0.5 or 1.0 mg/kg, delivered 5 min before the glucose challenge. At 75 days of age, pancreatic islets were isolated and exposed to glucose in the presence or absence of BR-b (1.0 or 5.0 μM). MSG-treated rats developed obesity, hyperinsulinemia, and insulin resistance. BR-b administration exacerbated glucose intolerance during the OGTT, particularly at the 1.0 mg/kg dose, with more pronounced effects observed in the CTL group. Insulin secretion from pancreatic islets was influenced by both obesity status and glucose concentration. In islets from CTL rats, BR-b (5 μM) reduced insulin release under non-stimulatory glucose conditions but enhanced insulin secretion at stimulatory glucose levels. Conversely, in islets from MSG-obese rats, BR-b exhibited an inhibitory effect on insulin release at basal glucose concentrations, while the insulinotropic response to high glucose was abolished. In summary, BR-b administration shortly before the OGTT impaired glucose tolerance and modulated insulin secretion from pancreatic islets in a glucose-dependent manner in non-obese rats. These effects were attenuated or absent in MSG-obese rats, indicating that hypothalamic obesity alters the metabolic responses to bombesin-related peptides.