First Author | Tirone TA | Year | 2003 |
Journal | Pancreas | Volume | 26 |
Issue | 3 | Pages | e67-73 |
PubMed ID | 12657967 | Mgi Jnum | J:185417 |
Mgi Id | MGI:5428675 | Doi | 10.1097/00006676-200304000-00025 |
Citation | Tirone TA, et al. (2003) Pancreatic somatostatin inhibits insulin secretion via SSTR-5 in the isolated perfused mouse pancreas model. Pancreas 26(3):e67-73 |
abstractText | INTRODUCTION: The function of pancreatic somatostatin in insulin secretion is controversial, and the receptor(s) mediating such event has not been exclusively investigated. AIM AND METHODOLOGY: To differentiate the specific role of SSTR5 in the mouse pancreas, we generated a mouse SSTR5 gene ablation model. Mice homozygous for the deletion (SSTR5-/-) and wild type (WT) littermate controls underwent whole pancreas perfusion to determine the effect of SSTR5 gene ablation on glucose-stimulated insulin secretion. The perfusion was done with and without octreotide added to the infusion buffer. Furthermore, pancreatic somatostatin was immunoneutralized by using a potent somatostatin monoclonal antibody to determine whether pancreatic somatostatin regulates insulin secretion in these mice. RESULTS: Results showed that at 3 months of age, there were no alterations in insulin secretion compared with WT controls. However, glucose-stimulated insulin secretion was significantly enhanced in 12-month-old SSTR5-/- mice compared with WT controls. The addition of octreotide to the perfusion significantly suppressed insulin secretion in WT controls, while it had no effect on SSTR5-/- mice. Immunoneutralization of pancreatic somatostatin resulted in enhanced glucose-stimulated insulin secretion in WT controls, but decreased levels of insulin secretion in SSTR5-/- mice. CONCLUSION: These results suggest that, in the mouse, pancreatic somatostatin regulates insulin secretion through SSTR5, and that the effect is age-specific. |