Effects of central neuromedin B and related peptides on blood glucose

Abstract

Bombesin (Bn), a peptide of amphibian origin, has been shown to induce hyperglycemia when injected centrally. In recent years, two families of Bn-like peptides have been isolated from the mammalian brain: the gastrin releasing peptide (GRP) type and neuromedin B (NB) type. Distinct receptor subtypes with different mRNAs have also been identified for NB versus GRP/Bn using hybridization and receptor binding studies. It is thus possible that those two families of peptides may display distinct pharmacological profiles. The objective of the current experiment was to determine whether the NB-like peptides could also affect blood glucose levels. The peptide analogs utilized were Bn, NB-10, NAcNB-10 and NB-32 (0, 0.031, 0.062, 0.31, 0.62, 3.1 nmol/3 μl; i.c.v.). Male rats, chronically implanted with 4th ventricular cannula, were injected with the various neuropeptide doses using the Latin square design. Blood samples were collected (120 μl) from the tail immediately preceeding and at 15, 30 and 60 min following peptide administration. Bn elevated glucose for over 60 min and this effect was maximal at 30 min. NB-10 and NAcNB-10 only slightly elevated plasma glucose. NB-32 elevated plasma glucose at all doses tested, the effect being evident up to 60 min at the highest dose. Our data indicate that at equimolar doses (0.31 nM) NB analogues elevate blood glucose with a lower efficacy than Bn ( Bn > NB-32 > NB-10 ≥ NAcNB-10 ). NB-32 appears more potent and efficacious than the other NB congeners used. Implications of these results in terms of higher affinity for the receptors and/or a longer biological half life are discussed.