Alterations in oral glucose‐stimulated insulin release in neuromedin B receptor knockout mice (LB768)

Abstract

Neuromedin B (NB) is a bombesin‐like peptide found in gastrointestinal tube and pancreas, among other tissues. It has been proposed that NB has a role in insulin secretion, either by a direct effect in pancreatic cells or acting as modulator of the release of gastrointestinal hormones that are incretins. However the relevance of NB and its receptor to insulin secretion and glucose homeostasis is still unclear. Glucose homeostasis in wild type (WT) and neuromedin B receptor knockout (NBR‐KO) mice was examined by measuring glucose and insulin levels at fasted and after oral glucose load states. Female NBR‐KO exhibited similar fasting basal glucose with a 48.4% lower insulinaemia (p<0.05) and lower HOMA (homeostasis model assessment of insulin resistance) index (50.5% lower, p<0.05). Additionally, they were more tolerant to oral glucose as demonstrated by the 18% lower area under the glucose curve (p<0.05). NBR‐KO mice also showed 45.6% less insulin serum levels than WT mice (p<0.05)15 minutes after an oral glucose load, even though blood glucose rose to similar levels in both groups. Male NBR‐KO mice exhibited a mild phenotype, but they also presented lower insulin serum levels 15 minutes after glucose gavage (26.8% lower, p<0.05). Single injection of NB, one hour previous to the oral glucose administration tended to induce higher serum insulin in WT mice, however the same did not occur in NBR‐KO mice. Collectively, data show that NBR‐KO mice have lower insulin response to oral glucose, together with a better glucose tolerance, suggesting that NB and its receptor are involved in insulin secretion by incretins and also, in insulin sensitivity.Grant Funding Source: Supported by: FAPERJ, CAPES and CNPq