The hypothalamus participates in the regulation of carbohydrate metabolism involving a feedback loop between the brain and the periphery in which glucose-sensitive hypothalamic areas appear to be involved. We have previously shown that a glucose injection (9 mg/kg) in the carotid artery toward the brain, in an amount that did not modify glycaemia, caused a rapid and transient increase in plasma insulin concentrations. To determine whether central insulin could influence this response, we investigated the change in central glucose-induced insulin secretion in intracerebroventricular (i.c.v) insulin-injected rats and in hyperinsulinaemic obese Zucker rats. Central glucose-induced insulin secretion was increased by 50% in i.c.v. insulin-injected rats compared to control rats. When a similar test was performed at a lower dose of glucose (3 mg/kg), a significant insulin secretion was observed only in rats submitted to a prior central insulin injection. These data indicate an increase in the brain response to glucose after insulin treatment. Using an identical lower glucose dose, we also demonstrated an enhanced brain glucose sensitivity in hyperinsulinaemic and insulin-resistant obese Zucker rats. Together, these results indicate that acute i.c.v. insulin or pathological hyperinsulinaemic state (i.e. obese Zucker rat) modulates the nervous control of insulin secretion by increasing the brain response to glucose.