Functions of pancreatic β cells and adipocytes in bombesin receptor subtype-3-deficient mice☆
Section snippets
Materials and methods
Animals. Male BRS-3-deficient mice [13] and male wild-type control littermates were used at the age of 12 weeks. The mice were given free access to food and water until the start of the experiments.
Islet isolation, insulin release, and proinsulin biosynthesis. Pancreatic islets were isolated by collagenase digestion as described previously [14]. For insulin-release experiments, islets were preincubated for 1 h in Krebs–Ringer buffer (KRB) containing 2.2 mM glucose and then challenged by 22 mM
Studies using pancreatic β cell
Because mice lacking functional BRS-3 develop the impairments of glucose tolerance and insulin tolerance as described [13], we intended to characterize the functions of both pancreatic β cells and adipose cells in this study. First, we studied both insulin secretion and proinsulin biosynthesis in pancreatic β cells. Fig. 1A shows the glucose responsiveness of insulin release from islets of BRS-3-deficient and wild-type control mice. There was no statistical difference among levels of insulin
Conclusion deduced from the two studies
The growth of islets in the pancreas was disturbed by the disruption of BRS-3, but insulin release and biosynthesis were preserved. On the other hand, the GLUT4 translocation system in the adipocytes was impaired by the disruption of BRS-3. Thus, the impairment of glucose metabolism observed in BRS-3-deficient mice may be the result of the impaired GLUT4 translocation in the adipocytes and the stress on β cells.
Acknowledgements
This work was supported by Grants-in-Aid for Scientific Research (C) 14570130 (to M.O.-I.) and (B) 15390108 (to S.N.) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.
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Bombesin Receptor Subtype-3 in Human Diseases
2019, Archives of Medical ResearchInsights into bombesin receptors and ligands: Highlighting recent advances
2015, PeptidesCitation Excerpt :Mice with GRPR disrupted demonstrated an increase in meal size consistent with a satiety signaling deficit [47,161,163]; those with NMBR knockouts initially had no effect on food intake or satiety found [247], however in a more recent study [259] they were found to have resistance to the development of diet induced obesity: and finally mice with BRS-3 disrupted developed obesity, hypertension, impaired glucose metabolism and insulin resistance [208,249]. This was accompanied by a reduced metabolic rate, hyperphagia and increased feeding efficacy, increased meal size, and alterations in glucose transport [129,161,162,193,208,243]. Studies show that mice, human rhesus and dog all have high expression of BRS-3 in the islets [82].
Human BRS-3 receptor: Functions/role in cell signaling pathways and glucose metabolism in obese or diabetic myocytes
2014, PeptidesCitation Excerpt :Moreover, it has been described that BRS-3 pathway contributes to the regulation of plasma insulin concentrations [19] and also, that the number and size of pancreatic islets, decreased in BRS-3-KO-mice, whereas insulin release and biosynthesis, in response to glucose were preserved. Therefore, this imbalance may cause an eventual stress on β-cells, which may lead to glucose intolerance in vivo [21]. Hyperphagia is a major factor, leading to increased body weight and hyperinsulinemia, in BRS-3 gene deletion mice.
Bombesin receptor subtype-3 (BRS-3), a novel candidate as therapeutic molecular target in obesity and diabetes
2013, Molecular and Cellular EndocrinologyCitation Excerpt :Those facts, allow us to affirm that not only BRS-3 is involved in the glucose-related effects but also its synthetic agonist. Moreover, GLUT-4 is the main membrane protein responsible for insulin-induced hexose uptake (Burant et al., 1991); when we examined GLUT-4 cytoplasmic protein in myocytes, the levels measured in normal subjects were unchanged compared with those in obese and T2D groups, as well as previously described in adipocytes from BRS-3 deficient mice respect to wild-type (Nakamichi et al., 2004). However, when membrane distribution of GLUT-4 protein was analyzed, markedly differences between the normal myocytes and the altered cells were observed.
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Abbreviations: ELISA, enzyme-linked immunosorbent assay; KRB, Krebs–Ringer buffer; PCR, polymerase chain reaction; SDS, sodium dodecyl sulfate; PAGE, polyacrylamide gel electrophoresis; VAMP-2, vesicle associated membrane protein-2; GLUT, facilitative glucose transporter; GRP-R, gastrin-releasing peptide receptor; NMB-R, neuromedin B receptor.