GLUTAMATE STIMULATES INSULIN-SECRETION AND IMPROVES GLUCOSE-TOLERANCEIN RATS

We previously showed in vitro that glutamate stimulates insulin releas e via an lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid recep tor. Here we address a more physiological question concerning the in v ivo effect of intravenously or orally administered glutamate on insuli nemia and glycemia in fed and fasted rats. In anesthetized fed rats, t he intravenous administration of glutamate at 9 and 30 mg/kg transient ly increased insulinemia in a dose-dependent manner. The insulin-secre tory effect of glutamate (9 mg/kg) was blocked by an antagonist of lph a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. In ane sthetized fasted rats, glutamate at 9 mg/kg was ineffective, but durin g an intravenous glucose tolerance test (0.5 g/kg), glutamate markedly potentiated insulin release and increased the glucose disappearance r ate. In conscious rats, the intragastric administration of glutamate a t 200 mg/kg elicited a transient insulin response in fed animals and h ad no effect in fasted animals but, during an oral glucose tolerance t est (1 g/kg), enhanced insulin secretion and reduced the hyperglycemia . Glutamate was effective at plasma concentrations of 200-300 mu M. In conclusion, intravenously and orally administered glutamate stimulate s insulin secretion in vivo via an excitatory amino acid receptor and improves glucose tolerance.