No abstract

A study was carried out to evaluate the acute effect of an intravenous injection of metformin on the fasting plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in 15 non-diabetic subjects. Metformin (1 g) was administered as a bolus in a peripheral vein and blood was sampled 2, 5, 10, 15 and 30 minutes after the drug injection. No significant change in fasting concentration of glucose nor in C-peptide, insulin, glucagon and growth hormone fasting levels was noticed. It is concluded that metformin does not possess an acute direct hypoglycaemic effect in non-diabetic subjects and does not acutely affect the basal activity of endocrine pancreas and pituitary gland in releasing insulin, glucagon and growth hormone.

The possible stimulatory effects of an intravenous infusion of increasing amounts of pituitary adenylate cyclase-activating polypeptide (PACAP) on anterior pituitary hormone secretions were evaluated in humans. Successively increasing doses of PACAP-38 (2, 4 and 8 pmol·kg^–1·min^–1; each dose for 20 min) were infused i.v. in 7 normal male subjects. On a different occasion, the same subjects were tested with vasoactive intestinal peptide (VIP; 4 pmol · kg^–1 · min^–1 for 60 min). Circulating GH, ACTH, PRL, TSH and gonadotropin concentrations were measured before PACAP infusion and every 20 min, just before increasing the infusion dose of PACAP. Blood samples were taken before and every 15 min after the beginning of VIP administration. Serum levels of GH, TSH and gonadotropins did not change during PACAP or VIP infusion. Circulating ACTH and PRL concentrations were not modified by the infusion of the lowest dose of PACAP, whereas they were significantly increased in a dose-response fashion when higher amounts of PACAP were given. PRL, but not ACTH levels were significantly increased by VIP infusion. These data show for the first time in humans that ACTH and PRL secretions from the anterior pituitary gland are stimulated by the systemic administration of PACAP. In addition, since VIP stimulated only PRL secretion, PACAP-induced ACTH release appears to be mediated by specific receptors.

The effect of synthetic substance P (SP), infused intravenously in doses of 0.5, 1 or 1.5 pmol/kg^–1/min^–1 over 60 min on ACTH/cortisol secretion was evaluated in 7 healthy men. SP tests and a control test with normal saline were randomly performed at weekly intervals. During tests, SP infusion did not produce untoward side effects or changes in blood pressure. Plasma ACTH and cortisol levels were not modified when normal saline or the lowest dose of SP were infused, whereas they were significantly increased in a dose-dependent fashion when higher amounts of SP were administered. Further studies were performed in another 7 healthy men to test the possible influence of GABAergic neurotransmission on the ACTH/cortisol response to SP. For this purpose, subjects were tested with SP (1.5 pmol/kg^–1/min^–1) alone and on a different occasion with SP after pretreatment with the GABAergic agent sodium valproate (200 mg 16, 8 and 1 h before the SP test). Again, the administration of SP induced a significant increase in plasma ACTH and cortisol levels. The pretreatment with sodium valproate completely abolished both ACTH and cortisol responses to SP. These data demonstrate for the first time in humans that the systemic infusion of SP stimulates ACTH/cortisol secretion, suggesting the involvement of a GABAergic mechanism in the regulation of the action of SP.