Mice with Deletion of Neuromedin B Receptor Exhibit Decreased Oral Glucose-Stimulated Insulin Release

Horm Metab Res. 2016 Dec;48(12):854-861. doi: 10.1055/s-0042-115643. Epub 2016 Oct 18.

Abstract

Neuromedin B (NB) and gastrin-releasing peptide (GRP) are bombesin-like peptides, found in the gastrointestinal tube and pancreas, among other tissues. Consistent data proposed that GRP stimulates insulin secretion, acting directly in pancreatic cells or in the release of gastrointestinal hormones that are incretins. However, the role of NB remains unclear. We examined the glucose homeostasis in mice with deletion of NB receptor (NBR-KO). Female NBR-KO exhibited similar fasting basal glucose with lower insulinemia (48.4%) and lower homeostasis model assessment of insulin resistance index (50.5%) than wild type (WT). Additionally, they were more tolerant to oral glucose, demonstrated by a decrease in the area under the glucose curve (18%). In addition, 15 min after an oral glucose load, female and male NBR-KO showed lower insulin serum levels (45.6 and 26.8%, respectively) than WT, even though blood glucose rose to similar levels in both groups. Single injection of NB, one hour before the oral glucose administration, tended to induce higher serum insulin in WT (28.9%, p=0.3), however the same did not occur in NBR-KO. They showed no changes in fasting insulin content in pancreatic islets by immunohistochemistry, however, the fasting serum levels of glucagon-like peptide, a potent incretin, exhibited a strong trend to reduction (40%, p=0.07). Collectively, mice with deletion of NB receptor have lower insulinemia, especially in response to oral glucose, and females also exhibited a better glucose tolerance, suggesting the involvement of NB and its receptor in regulation of insulin secretion induced by incretins, and also, in insulin sensitivity.

MeSH terms

  • Administration, Oral
  • Animals
  • Fasting
  • Female
  • Gene Deletion*
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1 / metabolism
  • Glucose / administration & dosage*
  • Glucose / pharmacology*
  • Glucose Tolerance Test
  • Homeostasis / drug effects
  • Insulin / metabolism*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / pathology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurokinin B / administration & dosage
  • Neurokinin B / analogs & derivatives
  • Neurokinin B / pharmacology
  • Receptors, Bombesin / deficiency
  • Receptors, Bombesin / metabolism*

Substances

  • Insulin
  • Receptors, Bombesin
  • Neurokinin B
  • neuromedin B
  • Glucagon-Like Peptide 1
  • Glucagon
  • Glucose